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 (Abeta) and cholesterol in vivo, we examined the effects of intracerebroventricular injection of Abeta(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 Abeta(1-42) resulted in deposition of this peptide, activation of astrocytes, decreased levels of the alpha7 and alpha4 protein subunits of the nAChR, and elevated expression of alpha7 mRNA, as well as impaired learning and spatial memory. A high-cholesterol diet activated astrocytes and, more importantly, potentiated the toxic effects of Abeta 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.
Liu
Ru-Yu
RY
Department of Pathology, Guiyang Medical University, Guizhou, People's Republic of China.
Gu
Ran
R
Qi
Xiao-Lan
XL
Zhang
Ting
T
Zhao
Yan
Y
He
Yan
Y
Pei
Jin-Jing
JJ
Guan
Zhi-Zhong
ZZ
D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002784:Cholesterol / Q000008:administration & dosage* / Q000097:blood; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology; D004041:Dietary Fats / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007276:Injections, Intraventricular / Q000379:methods; D018782:Maze Learning / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D016622:Silver Staining / Q000379:methods
D016229:Amyloid beta-Peptides; D004041:Dietary Fats; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; D021122:Protein Subunits; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; C075222:amyloid beta-protein (1-42); D002784:Cholesterol