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Chronic neuroinflammation in rats reproduces components of the neurobiology of Alzheimer''s disease |
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| Authors: | Beatrice Hauss-Wegrzyniak Pawel Dobrzanski James D Stoehr Gary L Wenk |
| Affiliation: | a Arizona Research Laboratories, Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, AZ, USA b Experimental Pharmacology Division, Cephalon, West Chester, PA, USA c Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Phoenix, AZ, USA |
| 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 μg/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-1β, tumor necrosis factor- and β-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. |
| Keywords: | Neuroinflammation Rat Basal forebrain Acetylcholine Alzheimer's disease Model |
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