Chronic brain inflammation leads to a decline in hippocampal NMDA-R1 receptors.
BACKGROUND: Neuroinflammation plays a prominent role in the progression of Alzheimer's disease and may be responsible for degeneration in vulnerable regions such as the hippocampus. Neuroinflammation is associated with elevated levels of extracellular glutamate and potentially an enhanced stimulation of glutamate N-methyl-D-aspartate receptors. This suggests that neurons that express these glutamate receptors might be at increased risk of degeneration in the presence of chronic neuroinflammation. METHODS: We have characterized a novel model of chronic brain inflammation using a slow infusion of lipopolysaccharide into the 4th ventricle of rats. This model reproduces many of the behavioral, electrophysiological, neurochemical and neuropathological changes associated with Alzheimer's disease. RESULTS: The current study demonstrated that chronic neuroinflammation is associated with the loss of N-methyl-D-aspartate receptors, as determined both qualitatively by immunohistochemistry and quantitatively by in vitro binding studies using [3H]MK-801, within the hippocampus and entorhinal cortex. CONCLUSION: The gradual loss of function of this critical receptor within the temporal lobe region may contribute to some of the cognitive deficits observed in patients with Alzheimer's disease.
Arizona Research Laboratories, Division of Neural Systems, Memory & Aging; University of Arizona, Tucson, AZ, USA. gary@nsma.arizona.edu
Susanna
S
Rosi
Victor
V
Ramirez-Amaya
Beatrice
B
Hauss-Wegrzyniak
Gary L
GL
Wenk