PMID- 27435080
OWN - NLM
STAT- MEDLINE
DCOM- 20170310
LR  - 20240209
IS  - 1466-1268 (Electronic)
IS  - 1355-8145 (Print)
IS  - 1355-8145 (Linking)
VI  - 21
IP  - 5
DP  - 2016 Sep
TI  - The involvement of homocysteine in stress-induced Abeta precursor protein 
      misprocessing and related cognitive decline in rats.
PG  - 915-26
LID - 10.1007/s12192-016-0718-0 [doi]
AB  - Chronic stress is a risk factor in the development of cognitive decline and even 
      Alzheimer's disease (AD), although its underlying mechanism is not fully 
      understood. Our previous data demonstrated that the level of homocysteine (Hcy) 
      was significantly elevated in the plasma of stressed animals, which suggests the 
      possibility that Hcy is a link between stress and cognitive decline. To test this 
      hypothesis, we compared the cognitive function, plasma concentrations of Hcy, and 
      the brain beta-amyloid (Abeta) level between rats with or without chronic unexpected 
      mild stress (CUMS). A lower performance by rats in behavioral tests indicated 
      that a significant cognitive decline was induced by CUMS. Stress also disturbed 
      the normal processing of Abeta precursor protein (APP) and resulted in the 
      accumulation of Abeta in the brains of rats, which showed a positive correlation 
      with the hyperhomocysteinemia (HHcy) that appeared in stressed rats. 
      Hcy-targeting intervention experiments were used to verify further the 
      involvement of Hcy in stress-induced APP misprocessing and related cognitive 
      decline. The results showed that diet-induced HHcy could mimic the cognitive 
      impairment and APP misprocessing in the same manner as CUMS, while Hcy reduction 
      by means of vitamin B complex supplements and betaine could alleviate the 
      cognitive deficits and dysregulation of Abeta metabolism in CUMS rats. Taken 
      together, the novel evidence from our present study suggests that Hcy is likely 
      to be involved in chronic stress-evoked APP misprocessing and related cognitive 
      deficits. Our results also suggested the possibility of Hcy as a target for 
      therapy and the potential value of vitamin B and betaine intake in the prevention 
      of stress-induced cognitive decline.
FAU - Xie, Fang
AU  - Xie F
AD  - Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping 
      Road, Haidian, Beijing, 100039, People's Republic of China.
FAU - Zhao, Yun
AU  - Zhao Y
AD  - Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping 
      Road, Haidian, Beijing, 100039, People's Republic of China.
FAU - Ma, Jing
AU  - Ma J
AD  - Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping 
      Road, Haidian, Beijing, 100039, People's Republic of China.
FAU - Gong, Jing-Bo
AU  - Gong JB
AD  - Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping 
      Road, Haidian, Beijing, 100039, People's Republic of China.
FAU - Wang, Shi-Da
AU  - Wang SD
AD  - Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping 
      Road, Haidian, Beijing, 100039, People's Republic of China.
FAU - Zhang, Liang
AU  - Zhang L
AD  - Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping 
      Road, Haidian, Beijing, 100039, People's Republic of China.
FAU - Gao, Xiu-Jie
AU  - Gao XJ
AD  - Institute of Health and Environmental Medicine, Tianjin, 300050, People's 
      Republic of China.
FAU - Qian, Ling-Jia
AU  - Qian LJ
AD  - Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping 
      Road, Haidian, Beijing, 100039, People's Republic of China. newjia@vip.sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160719
PL  - Netherlands
TA  - Cell Stress Chaperones
JT  - Cell stress & chaperones
JID - 9610925
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Alzheimer Disease/*blood/psychology
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Cognitive Dysfunction/*blood/psychology
MH  - Hippocampus/metabolism
MH  - Homocysteine/*blood
MH  - Male
MH  - Protein Processing, Post-Translational
MH  - Rats, Sprague-Dawley
MH  - Stress, Psychological/*blood/complications
PMC - PMC5003809
OTO - NOTNLM
OT  - Beta-amyloid
OT  - Chronic unexpected mild stress
OT  - Cognitive decline
OT  - Homocysteine
COIS- Compliance with ethical standards Conflicts of interest The authors declare that 
      they have no competing interests.
EDAT- 2016/07/21 06:00
MHDA- 2017/03/11 06:00
PMCR- 2017/03/01
CRDT- 2016/07/21 06:00
PHST- 2016/05/24 00:00 [received]
PHST- 2016/07/01 00:00 [accepted]
PHST- 2016/07/01 00:00 [revised]
PHST- 2017/03/01 00:00 [pmc-release]
PHST- 2016/07/21 06:00 [entrez]
PHST- 2016/07/21 06:00 [pubmed]
PHST- 2017/03/11 06:00 [medline]
AID - S1355-8145(23)00491-1 [pii]
AID - 718 [pii]
AID - 10.1007/s12192-016-0718-0 [doi]
PST - ppublish
SO  - Cell Stress Chaperones. 2016 Sep;21(5):915-26. doi: 10.1007/s12192-016-0718-0. 
      Epub 2016 Jul 19.