Systems neuroscienceChemokine receptor 5 antagonist d-Ala-peptide T-amide reduces microglia and astrocyte activation within the hippocampus in a neuroinflammatory rat model of Alzheimer's disease
Section snippets
Subjects
Eighteen male, three month old, F-344 (Harlan Sprague–Dawley, Indianapolis, IN, USA) were assigned to three groups: 1) artificial cerebrospinal fluid (aCSF)-infused (n=6); 2) LPS-infused, vehicle-treated (n=6); 3) LPS-infused, DAPTA-treated (0.01mg/kg/day, s.c, n=6). LPS (1.0μg/μl) or was chronically infused (0.25μl/h for 14 days) through a cannula implanted into the 4th ventricle of the brain that was attached to an osmotic minipump as previously described (Hauss-Wegrzyniak et al., 1998,
Results
Chronic infusion of LPS into the 4th ventricle of young rats for 2 weeks was well tolerated by all rats. Initially after surgery, all LPS-infused rats lost a few grams of weight. Within a few days, however, most rats had regained weight and continued to gain weight normally for the duration of the study (Rosi et al., 2005).
Discussion
Chronic infusion of LPS into the 4th ventricle produced an extensive inflammatory reaction throughout the brain, particularly within the hippocampus and temporal lobe regions. The inflammatory response was characterized by a significant increase in the number of reactive microglial cells, a marked hypertrophy of numerous astrocytes and an elevation in the NFkB staining. The effects of LPS infusion upon microglial and astrocyte activation were consistent with our previous reports (
Acknowledgments
Supported by the U.S. Public Health Service, Contract grant number AG10546 and the Alzheimer's Association, IIRG-01-2654 to G.L.W.
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