PMID- 33737111 OWN - NLM STAT- MEDLINE DCOM- 20210914 LR - 20210914 IS - 1873-6351 (Electronic) IS - 0278-6915 (Linking) VI - 151 DP - 2021 May TI - Effects of alcohol intake on cognitive function and beta-amyloid protein in APP/PS1 transgenic mice. PG - 112105 LID - S0278-6915(21)00138-1 [pii] LID - 10.1016/j.fct.2021.112105 [doi] AB - To investigate the effects of alcohol intake on cognitive function and beta-amyloid protein (Abeta) in APP/PS1 double-transgenic mice with Alzheimer's disease (AD). Sixty APP/PS1 transgenic male mice were randomized into seven groups: control group, 0.5% alcohol group, 1% alcohol group, 2% alcohol group, 3% alcohol group, and 4% alcohol group, with 10 non-transgenic B6C3F1 mice of the same genetic background as the negative control group. All mice were pair-fed a liquid diet containing alcohol before assessment of learning and memory using the Y-maze test, and of Abeta content and related enzyme activity on them. Immunohistochemistry was used to detect the expression of Abeta(1-42), Abeta(1-40), and beta-amyloid precursor protein (beta-APP) in the cerebral cortex. 3%, and 4% alcohol intake significantly impaired the learning and memory abilities. 2%, 3%, and 4% alcohol groups indicated a remarkable change in Abeta(1-42) content, alpha-secretase and gamma-secretase activities in the hippocampus, and beta-APP in the cortex; 3% and 4% alcohol groups showed a significant increase in Abeta(1-42) content, beta-site amyloid cleavage enzyme 1 (BACE1) activity, and a significant decrease in alpha-secretase activity in the hippocampus or cortex; 2% and 3% alcohol groups showed a significant increase in Abeta(1-40) content in the hippocampus or cortex; and 2%, 3%, and 4% alcohol groups showed an increase in the expression of Abeta(1-42), Abeta(1-40,) and beta-APP in the cortex; 1% alcohol groups showed a significant decline in the levels of Abeta(1-42), Abeta(1-40), beta-APP, and BACE1 activity in the hippocampus, and gamma-secretase activity in the hippocampus and cortex, and 1% alcohol group showed a significant increase of alpha-secretase activity in the hippocampus. Besides, 0.5% alcohol showed statistically significant effects on the reduction of BACE1 and gamma-secretase activities in the hippocampus. Long-term intake of high-dose alcohol can induce cognitive deficits and improve the activity of beta-APP decomposition-related enzymes, increase Abeta content and deposition, and initiate AD progression, while long-term intake of low-dose alcohol can antagonize excessive production of Abeta and slow down AD progression. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Gong, Yu-Shi AU - Gong YS AD - School of Food Science, Guangdong Pharmaceutical University, Zhongshan, 528458, China. Electronic address: tortoise39@163.com. FAU - Hou, Fang-Li AU - Hou FL AD - School of Food Science, Guangdong Pharmaceutical University, Zhongshan, 528458, China. FAU - Guo, Juan AU - Guo J AD - School of Food Science, Guangdong Pharmaceutical University, Zhongshan, 528458, China. FAU - Lin, Lin AU - Lin L AD - School of Food Science, Guangdong Pharmaceutical University, Zhongshan, 528458, China. FAU - Zhu, Fu-Yong AU - Zhu FY AD - School of Food Science, Guangdong Pharmaceutical University, Zhongshan, 528458, China. LA - eng PT - Journal Article DEP - 20210316 PL - England TA - Food Chem Toxicol JT - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JID - 8207483 RN - 0 (Amyloid beta-Peptides) RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Presenilin-1) RN - 0 (presenilin 1, mouse) RN - 3K9958V90M (Ethanol) RN - EC 3.4.- (Amyloid Precursor Protein Secretases) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 3.4.23.46 (Bace1 protein, mouse) SB - IM MH - *Alcohol Drinking MH - Amyloid Precursor Protein Secretases/metabolism MH - Amyloid beta-Peptides/*metabolism MH - Amyloid beta-Protein Precursor/*genetics MH - Animals MH - Aspartic Acid Endopeptidases/metabolism MH - Brain/enzymology/metabolism MH - *Cognition MH - Dose-Response Relationship, Drug MH - Ethanol/administration & dosage MH - Male MH - Mice MH - Mice, Transgenic MH - Presenilin-1/*genetics OTO - NOTNLM OT - Alcohol OT - Alzheimer's disease OT - Brain OT - Learning and memory OT - beta-amyloid protein EDAT- 2021/03/20 06:00 MHDA- 2021/09/15 06:00 CRDT- 2021/03/19 06:17 PHST- 2020/10/30 00:00 [received] PHST- 2021/02/08 00:00 [revised] PHST- 2021/03/05 00:00 [accepted] PHST- 2021/03/20 06:00 [pubmed] PHST- 2021/09/15 06:00 [medline] PHST- 2021/03/19 06:17 [entrez] AID - S0278-6915(21)00138-1 [pii] AID - 10.1016/j.fct.2021.112105 [doi] PST - ppublish SO - Food Chem Toxicol. 2021 May;151:112105. doi: 10.1016/j.fct.2021.112105. Epub 2021 Mar 16.