Human amyloid beta-induced neuroinflammation is an early event in neurodegeneration.

Abstract

Using a human amyloid beta (Abeta) intracerebroventricular infusion mouse model of Alzheimer's disease-related injury, we previously demonstrated that systemic administration of a glial activation inhibitor could suppress neuroinflammation, prevent synaptic damage, and attenuate hippocampal-dependent behavioral deficits. We report that Abeta-induced neuroinflammation is an early event associated with onset and progression of pathophysiology, can be suppressed by the glial inhibitor over a range of intervention start times, and is amenable to suppression without inhibiting peripheral tissue inflammatory responses. Specifically, hippocampal neuroinflammation and neurodegeneration occur in close time proximity at 4-6 weeks after the start of infusion. Intraperitoneal administration of inhibitor for 2-week intervals starting at various times after initiation of Abeta infusion suppresses progression of pathophysiology. The glial inhibitor is a selective suppressor of neuroinflammation, in that it does not block peripheral tissue production of proinflammatory cytokines or markers of B- and T-cell activation after a systemic lipopolysaccharide challenge. These results support a causal link between neuroinflammation and neurodegeneration, have important implications for future therapeutic development, and provide insight into the relative time window for targeting neuroinflammation with positive neurological outcomes.

• Authors: Jeffrey M Craft, D Martin Watterson, Linda J Van Eldik
• Journal: Glia (Glia) Vol. 53 Issue 5 Pg. 484-90 (Apr 01 2006) ISSN: 0894-1491 [Print] United States
• PMID: 16369931 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2005 Wiley-Liss, Inc.

Chemical References

• Amyloid beta-Peptides
• Biomarkers
• Interleukin-1
• Lipopolysaccharides
• MW01 070C
• Pyridazines
• Tumor Necrosis Factor-alpha

Topics

• Amyloid beta-Peptides (toxicity)
• Animals
• B-Lymphocytes (pathology)
• Biomarkers
• Brain (pathology)
• Brain Chemistry (drug effects)
• Female
• Flow Cytometry
• Hippocampus (metabolism, pathology)
• Inflammation (pathology)
• Interleukin-1 (metabolism)
• Lipopolysaccharides (toxicity)
• Mice
• Mice, Inbred C57BL
• Neurodegenerative Diseases (pathology)
• Peripheral Nerves (cytology, pathology)
• Peripheral Nervous System Diseases (pathology)
• Pyridazines (pharmacology)
• T-Lymphocytes (pathology)
• Tumor Necrosis Factor-alpha (metabolism)