Research

Microglial activation in the hippocampus of hypercholesterolemic rabbits occurs independent of increased amyloid production

Qing-Shan Xue¹ , D Larry Sparks² and Wolfgang J Streit¹

¹  Department of Neuroscience, University of Florida College of Medicine and McKnight Brain Institute, 100 Newell Drive, Gainesville FL 32611, USA

²  Roberts Laboratory for Neurodegenerative Disease Research, Sun Health Research Institute, Sun City, AZ, USA

author email corresponding author email

Journal of Neuroinflammation 2007, 4:20doi:10.1186/1742-2094-4-20

Published:	24 August 2007

Abstract

Background

Rabbits maintained on high-cholesterol diets are known to show increased immunoreactivity for amyloid beta protein in cortex and hippocampus, an effect that is amplified by presence of copper in the drinking water. Hypercholesterolemic rabbits also develop sporadic neuroinflammatory changes. The purpose of this study was to survey microglial activation in rabbits fed cholesterol in the presence or absence of copper or other metal ions, such as zinc and aluminum.

Methods

Vibratome sections of the rabbit hippocampus and overlying cerebral cortex were examined for microglial activation using histochemistry with isolectin B₄ from Griffonia simplicifolia. Animals were scored as showing either focal or diffuse microglial activation with or without presence of rod cells.

Results

Approximately one quarter of all rabbits fed high-cholesterol diets showed evidence of microglial activation, which was always present in the hippocampus and not in the cortex. Microglial activation was not correlated spatially with increased amyloid immunoreactivity or with neurodegenerative changes and was most pronounced in hypercholesterolemic animals whose drinking water had been supplemented with either copper or zinc. Controls maintained on normal chow were largely devoid of neuroinflammatory changes, but revealed minimal microglial activation in one case.

Conclusion

Because the increase in intraneuronal amyloid immunoreactivity that results from administration of cholesterol occurs in both cerebral cortex and hippocampus, we deduce that the microglial activation reported here, which is limited to the hippocampus, occurs independent of amyloid accumulation. Furthermore, since neuroinflammation occurred in the absence of detectable neurodegenerative changes, and was also not accompanied by increased astrogliosis, we conclude that microglial activation occurs because of metabolic or biochemical derangements that are influenced by dietary factors.