Decreased nicotinic receptors and cognitive deficit in rats intracerebroventricularly injected with beta-amyloid peptide(1-42) and fed a high-cholesterol diet

To investigate whether the changes in nicotinic receptors (nAChRs) and in learning and memory associated with Alzheimer's disease (AD) are influenced by both beta-amyloid peptide (A beta) and cholesterol in vivo, we examined the effects of intracerebroventricular injection of A beta(1-42) and/or a high-cholesterol diet on brain levels of nAChRs and learning and memory in rats. The levels of nAChR subunit proteins and the corresponding mRNA were measured by Western blotting and RT-PCR, respectively; and learning and memory were evaluated with the Morris Water Maze examination. Injection of A beta(1-42) resulted in deposition of this peptide, activation of astrocytes, decreased levels of the alpha 7 and alpha 4 protein subunits of the nAChR, and elevated expression of alpha 7 mRNA, as well as impaired learning and spatial memory. A high-cholesterol diet activated astrocytes and, more importantly, potentiated the toxic effects of A beta on nAChR subunit levels and on learning and memory. These findings may be highly relevant to the mechanisms underlying the cognitive deficits associated with AD. (c) 2007 Wiley-Liss, Inc.