Alzheimer's Disease and Methanol Toxicity (Part 2): Lessons from Four Rhesus Macaques (Macaca mulatta) Chronically Fed Methanol

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	Alzheimer's Disease and Methanol Toxicity (Part 2): Lessons from Four Rhesus Macaques (Macaca mulatta) Chronically Fed Methanol
	Yang MF 1,5; Miao JY 2,5; Rizak J 1,5; Zhai RW 1,5; Wang ZB 1; Huma T 1; Li T 2,5; Zheng N 1,5; Wu SH 1,5; Zheng YW 1
刊名	JOURNAL OF ALZHEIMERS DISEASE
	2014
卷号	41 期号:4 页码:1131-1147
关键词	disease progression formaldehyde methanol toxicity tau Alzheimer's disease amyloid plaque formation cognitive impairment
通讯作者	herq@sun5.ibp.ac.cn ; xthu@mail.kiz.ac.cn
英文摘要	A recently established link between formaldehyde, a methanol metabolite, and Alzheimer's disease (AD) pathology has provided a new impetus to investigate the chronic effects of methanol exposure. This paper expands this investigation to the non-human primate, rhesus macaque, through the chronic feeding of young male monkeys with 3% methanol ad libitum. Variable Spatial Delay Response Tasks of the monkeys found that the methanol feeding led to persistent memory decline in the monkeys that lasted 6 months beyond the feeding regimen. This change coincided with increases in tau protein phosphorylation at residues T181 and S396 in cerebrospinal fluid during feeding as well as with increases in tau phosphorylated aggregates and amyloid plaques in four brain regions postmortem: the frontal lobe, parietal lobe, temporal lobe, and the hippocampus. Tau phosphorylation in cerebrospinal fluid was found to be dependent on methanol feeding status, but phosphorylation changes in the brain were found to be persistent 6 months after the methanol feeding stopped. This suggested the methanol feeding caused long-lasting and persistent pathological changes that were related to AD development in the monkey. Most notably, the presence of amyloid plaque formations in the monkeys highlighted a marked difference in animal systems used in AD investigations, suggesting that the innate defenses in mice against methanol toxicity may have limited previous investigations into AD pathology. Nonetheless, these findings support a growing body of evidence that links methanol and its metabolite formaldehyde to AD pathology.
收录类别	SCI
资助信息	This study was supported by the “Strategic Priority Research Program-B” of the Chinese Academy of Science (Grant No. XDB02020000), the 973 program of the Chinese Government (2012CB825500, 2011CB707800, 2010CB912303, 2012CB911004), the 863 program of the Chinese Government (2012AA020701), the following grants from the Chinese Academy of Science (KSCX2- EW-J-23, KSCX2-EW-R-11 and KSCX2-EW-R13), and the National Science Foundation of China, NSFC (91332120, 31271167, 31271168, 81271495, 31070963, 31070965).
语种	英语
WOS记录号	WOS:000340488400012
公开日期	2014-10-21
内容类型	期刊论文
源URL	[http://159.226.149.42:8088/handle/152453/8122]
专题	昆明动物研究所_神经系统编码昆明动物研究所_动物模型与人类重大疾病机理重点实验室昆明动物研究所_认知障碍病理学昆明动物研究所_中国科学院昆明灵长类研究中心
作者单位	1.KeyLaboratoryofAnimalModelsandHumanDiseaseMechanismsoftheChineseAcademyofSciences&Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, P.R. Chin 2.State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, P.R. China 3.Kunming Primate Research Center of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, P.R. China 4.Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan, P.R. China 5.University of the Chinese Academy of Sciences, Beijing, P.R. China
推荐引用方式 GB/T 7714	Yang MF,Miao JY,Rizak J,et al. Alzheimer's Disease and Methanol Toxicity (Part 2): Lessons from Four Rhesus Macaques (Macaca mulatta) Chronically Fed Methanol[J]. JOURNAL OF ALZHEIMERS DISEASE,2014,41(4):1131-1147.
APA	Yang MF.,Miao JY.,Rizak J.,Zhai RW.,Wang ZB.,...&Hu XT[*].(2014).Alzheimer's Disease and Methanol Toxicity (Part 2): Lessons from Four Rhesus Macaques (Macaca mulatta) Chronically Fed Methanol.JOURNAL OF ALZHEIMERS DISEASE,41(4),1131-1147.
MLA	Yang MF,et al."Alzheimer's Disease and Methanol Toxicity (Part 2): Lessons from Four Rhesus Macaques (Macaca mulatta) Chronically Fed Methanol".JOURNAL OF ALZHEIMERS DISEASE 41.4(2014):1131-1147.