PMID- 29401634
OWN - NLM
STAT- MEDLINE
DCOM- 20190131
LR  - 20220408
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 32
IP  - 7
DP  - 2018 Jul
TI  - Formaldehyde induces diabetes-associated cognitive impairments.
PG  - 3669-3679
LID - 10.1096/fj.201701239R [doi]
AB  - Patients with type 2 diabetes mellitus (T2DM) often develop cognitive impairments 
      and have an increased risk of developing Alzheimer's disease. Hyperglycemia is a 
      major characteristic of T2DM, but how elevated glucose levels lead to cognitive 
      decline remains elusive. Here, we report that patients with T2DM and mutations in 
      the formaldehyde (FA)-degrading enzyme aldehyde dehydrogenase 2 ( ALDH2) gene had 
      higher levels of FA and more severe dementia. Injection of FA induced 
      hyperglycemia and cognitive deficits in rats. Ablation of gene expression of 
      ALDH2, the main enzyme to oxidize FA, resulted in abnormally high levels of 
      hippocampal FA, leading to hyperglycemia and cognitive impairments as well as 
      potentiating streptozotocin-induced diabetes development in ALDH2 knockout mice. 
      We found that FA interacts with insulin to form FA-insulin adducts, and these 
      FA-insulin adducts caused insulin deficiency, contributing to memory decline in 
      diabetic rodent models. Reduction of FA by transgenic overexpression of human 
      ALDH2 attenuates hyperglycemia and alleviates cognitive deficits in diabetic 
      mouse models. These findings suggest that excess FA plays a critical role in 
      mediating diabetes-related dementia. Targeting FA and its metabolizing enzyme 
      ALDH2 may be a valid approach for preventing and treating dementia in diabetes 
      mellitus.-Tan, T., Zhang, Y., Luo, W., Lv, J., Han, C., Hamlin, J. N. R., Luo, 
      H., Li, H., Wan, Y., Yang, X., Song, W., Tong, Z. Formaldehyde induces 
      diabetes-associated cognitive impairments.
FAU - Tan, Tao
AU  - Tan T
AD  - Alzheimer's Disease Center, Beijing Institute for Brain Disorders, Capital 
      Medical University, Beijing, China.
AD  - Sichuan Provincial Hospital for Women and Children, Chengdu, China.
FAU - Zhang, Yun
AU  - Zhang Y
AD  - Department of Psychiatry, Townsend Family Laboratories, The University of British 
      Columbia, Vancouver, British Columbia, Canada.
FAU - Luo, Wenhong
AU  - Luo W
AD  - Central Laboratory, Shantou University Medical College, Guangdong, China.
FAU - Lv, Jihui
AU  - Lv J
AD  - Beijing Geriatric Hospital, Beijing, China.
FAU - Han, Chanshuai
AU  - Han C
AD  - Montreal Neurological Institute, McGill University, Quebec, Canada.
FAU - Hamlin, Jason N R
AU  - Hamlin JNR
AD  - Montreal Neurological Institute, McGill University, Quebec, Canada.
FAU - Luo, Hongjun
AU  - Luo H
AD  - Central Laboratory, Shantou University Medical College, Guangdong, China.
FAU - Li, Hui
AU  - Li H
AD  - Central Laboratory, Shantou University Medical College, Guangdong, China.
FAU - Wan, You
AU  - Wan Y
AD  - Department of Neurobiology, School of Basic Medical Sciences, Neuroscience 
      Research Institute, Peking University, Beijing, China.
FAU - Yang, Xu
AU  - Yang X
AD  - Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation 
      and Integrative Biology, College of Life Sciences, Central China Normal 
      University, Wuhan, China.
FAU - Song, Weihong
AU  - Song W
AD  - Department of Psychiatry, Townsend Family Laboratories, The University of British 
      Columbia, Vancouver, British Columbia, Canada.
FAU - Tong, Zhiqian
AU  - Tong Z
AD  - Alzheimer's Disease Center, Beijing Institute for Brain Disorders, Capital 
      Medical University, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180201
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Insulin)
RN  - 1HG84L3525 (Formaldehyde)
RN  - EC 1.2.1.3 (ALDH2 protein, human)
RN  - EC 1.2.1.3 (Aldehyde Dehydrogenase, Mitochondrial)
SB  - IM
MH  - Aged
MH  - Aldehyde Dehydrogenase, Mitochondrial/*genetics/metabolism
MH  - Animals
MH  - Cognitive Dysfunction/*etiology
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Female
MH  - Formaldehyde/blood/*toxicity/urine
MH  - Humans
MH  - Insulin/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mutation
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - ALDH2
OT  - Alzheimer
OT  - dementia
OT  - hyperglycemia
EDAT- 2018/02/07 06:00
MHDA- 2019/02/01 06:00
CRDT- 2018/02/07 06:00
PHST- 2018/02/07 06:00 [pubmed]
PHST- 2019/02/01 06:00 [medline]
PHST- 2018/02/07 06:00 [entrez]
AID - 10.1096/fj.201701239R [doi]
PST - ppublish
SO  - FASEB J. 2018 Jul;32(7):3669-3679. doi: 10.1096/fj.201701239R. Epub 2018 Feb 1.