Altered expression of Abeta metabolism-associated molecules from D-galactose/AlCl(3) induced mouse brain.
Cerebral deposition of amyloid-beta peptide (Abeta) is a critical feature of Alzheimer's disease (AD). Either aluminium trichloride (Al) or D-galactose (D-gal) induces Abeta overproduction in rat or mouse brain and has been used to produce models of aging and AD. Here it is shown that mice treated with Al plus D-gal represent a good model of AD with altered expression of Abeta metabolism-associated molecules. The work shows that Al/D-gal causes memory impairment and high Abeta levels in the cortex (Co) and hippocampus (Hi). Then, we found that beta-site APP cleavage enzyme 1 (BACE1) was increased in mouse Co and Hi. Al or Al plus D-gal suppressed mRNA of the low-density lipoprotein receptor-related protein 1(LRP1). D-gal also decreased the LRP expression in Hi, but not in Co. However, Al/D-gal did not affect the receptor for advanced glycation end products (RAGE) expression in mouse brains. Furthermore, Al/D-gal reduced the expression of neprilysin (NEP), but not the insulin degrading enzyme (IDE). This study indicates that Al/D-gal affects the expression of Abeta metabolism-associated molecules that are responsible for Abeta deposition during AD, suggesting that this mouse model can be a useful model for studying the mechanisms and biomarkers of AD and for drug screening.
Luo
Yun
Y
Department of Neurology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, PR China.
Niu
Fengnan
F
Sun
Zongzheng
Z
Cao
Wangsen
W
Zhang
Xin
X
Guan
Dening
D
Lv
Zhimai
Z
Zhang
Bing
B
Xu
Yun
Y
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology*; D005690:Galactose / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D008568:Memory / Q000187:drug effects; D051379:Mice; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism
D017607:Aluminum Compounds; D016229:Amyloid beta-Peptides; D002712:Chlorides; D011973:Receptors, LDL; D000077410:Aluminum Chloride; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D015260:Neprilysin; D005690:Galactose