Comparative effects of EtOH consumption and thiamine deficiency on cognitive impairment, oxidative damage, and β-amyloid peptide overproduction in the brain.
The effects of chronic EtOH consumption, associated or not with thiamine deficiency (TD), on cognitive impairment, oxidative damage, and β-amyloid (Aβ) peptide accumulation in the brain were investigated in male C57BL/6 mice. We established an alcoholic mouse model by feeding an EtOH liquid diet, a TD mouse model by feeding a thiamine-depleted liquid diet, and an EtOH treatment associated with TD mouse model by feeding a thiamine-depleted EtOH liquid diet for 7 weeks. The learning and memory functions of the mice were detected through the Y-maze test. Biochemical parameters were measured using corresponding commercial kits. The Aβ expression in the hippocampus was observed by immunohistochemical staining. Several results were obtained. First, EtOH significantly reduced cognitive function by significantly decreasing the Glu content in the hippocampus; increasing the AChE activity in the cortex; and reducing the thiamine level, and superoxide dismutase (SOD), glutathione peroxidase (GPx), and choline acetyltransferase (ChAT) activities in both the hippocampus and cortex. The treatment also increased the levels of malondialdehyde (MDA), protein carbonyl, 8-hydroxydeoxyguanosine (8-OHdG), and nitric oxide (NO) and the activities of total nitric oxide synthase (tNOS), inducible nitric oxide synthase (iNOS), and monoamine oxidase B (MAO-B). Furthermore, EtOH enhanced the expression levels of Aβ1-42and Aβ1-40in the hippocampus. Second, TD induced the same dysfunctions caused by EtOH in the biochemical parameters, except for learning ability, 8-OHdG content, and GPx, tNOS, and AChE activities in the cortex. Third, the modification of MDA, protein carbonyl and NO levels, and GPx, iNOS, ChAT, and MAO-B activities in the brain induced by chronic EtOH treatment associated with TD was greater than that induced by EtOH or TD alone. The synergistic effects of EtOH and TD on Aβ1-40and Glu release, as well as on SOD activity, depended on their actions on the hippocampus or cortex. These findings suggest that chronic EtOH consumption can induce TD, cognitive impairment, Aβ accumulation, oxidative stress injury, and neurotransmitter metabolic abnormalities. Furthermore, the association of chronic EtOH consumption with TD causes dramatic brain dysfunctions with a severe effect on the brain.
School of Food Science, Guangdong Pharmaceutical University, Zhongshan 528458, China. Electronic address: tortoise39@163.com.
Yu-Shi
YS
Gong
School of Food Science, Guangdong Pharmaceutical University, Zhongshan 528458, China.
Kun
K
Hu
School of Food Science, Guangdong Pharmaceutical University, Zhongshan 528458, China.
Lu-Qi
LQ
Yang
School of Food Science, Guangdong Pharmaceutical University, Zhongshan 528458, China.
Juan
J
Guo
School of Food Science, Guangdong Pharmaceutical University, Zhongshan 528458, China.
Yong-Qing
YQ
Gao
School of Food Science, Guangdong Pharmaceutical University, Zhongshan 528458, China.
Feng-Lin
FL
Song
School of Food Science, Guangdong Pharmaceutical University, Zhongshan 528458, China.
Fang-Li
FL
Hou
School of Food Science, Guangdong Pharmaceutical University, Zhongshan 528458, China.
Cui-Yi
CY
Liang
D000428:Alcohol Drinking; D000437:Alcoholism / Q000378:metabolism* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000502:physiology*; D003072:Cognition Disorders / Q000378:metabolism* / Q000523:psychology; D004035:Diet Therapy; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage*; D006801:Humans; D007858:Learning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D013831:Thiamine; D013832:Thiamine Deficiency / Q000378:metabolism* / Q000523:psychology; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D009569:Nitric Oxide; D000431:Ethanol; D008995:Monoamine Oxidase; D013831:Thiamine
Aβ; Brain; Cognitive impairment; EtOH consumption; Oxidative stress; Thiamine deficiency