Abstract
BackgroundNeuroinflammation 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.MethodsWe 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.ResultsThe 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.ConclusionThe 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.
Highlights
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
We have developed a model of chronic brain inflammation using a slow LPS infusion into the 4th ventricle of rats that reproduces many of the behavioral, electrophysiological, neurochemical and neuropathological changes associated with AD [14,15], including the presence of activated microglia within the hippocampus and entorhinal cortex (EC), impaired long term potentiation in the dentate gyrus, impaired learning and memory, and a significant loss of CA3 hippocampal pyramidal cells and entorhinal pyramidal neurons in layers II & III [6,7,8,9,25,26,27]
Because so little is known regarding the consequences of long term neuroinflammation produced in this model, it is impossible to be certain whether the loss of NMDA glutamate receptors that we report is selective for this brain region or this particular receptor
Summary
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. Neuroinflammation plays a prominent role in the progression of Alzheimer's disease [AD, [1,2]] Brain regions, those involved in learning and memory, which demonstrate the greatest degree of microglia cell activation early in the disease show the highest rate of atrophy and pathology [3]. The number of NMDA receptors within the hippocampus, EC and basal (page number not for citation purposes)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
