PMID- 32345540
OWN - NLM
STAT- MEDLINE
DCOM- 20210401
LR  - 20210401
IS  - 1618-0631 (Electronic)
IS  - 0344-0338 (Linking)
VI  - 216
IP  - 6
DP  - 2020 Jun
TI  - Synaptic remodeling and reduced expression of the transcription factors, HES1 and 
      HES5, in the cortex neurons of cognitively impaired hyperhomocysteinemic mice.
PG  - 152953
LID - S0344-0338(20)30300-9 [pii]
LID - 10.1016/j.prp.2020.152953 [doi]
AB  - Hyperhomocysteinemia (HHcy) is associated with cognitive impairment and 
      neurodegenerative diseases. The synaptic ultrastructure and the expression of 
      hairy enhancer of split (HES) genes are involved in cognitive impairment induced 
      by HHcy, but their precise role remains unclear. The present study aimed to 
      measure synaptic remodeling and the expression of HES1 and HES5 in the cortex 
      neurons of mice with HHcy to clarify their role in cognitive impairment. Mild 
      HHcy was induced in ApoE(-/-) mice receiving a high-methionine diet. The correct 
      response percentage, latency, and distance traveled in the mice with HHcy 
      decreased compared with those of non-HHcy control mice (P < 0.05). There was no 
      difference in the neuronal counts and the mean optical density of Nissl bodies in 
      the frontal cortex of HHcy and non-HHcy mice. Increased apoptosis rates and 
      numbers of autophagosomes were observed in the HHcy mice by TUNEL staining and 
      electron microscopy, respectively, compared to those in the control group (P < 
      0.05). There was a significant increase in the area of postsynaptic density and 
      size variation of synaptic vesicles in the HHcy group compared to that in the 
      control (P < 0.05). Decreased expression of HES1 and HES5 was observed by western 
      blotting and immunostaining in the HHcy group compared to that in the control (P 
      < 0.05). Collectively, these results suggest that increased autophagy, apoptosis, 
      synaptic remodeling, and downregulation of hes1 and hes5 are involved in the 
      cognitive impairment induced by hyperhomocysteinemia.
CI  - Copyright (c) 2020. Published by Elsevier GmbH.
FAU - Zhang, Jing-Wen
AU  - Zhang JW
AD  - Institute For Cancer Research, School Of Basic Medical Science, Health Science 
      Center, Xi'an Jiaotong University, Xi'an, 710061, China; School of Basic Medical 
      Science, Ningxia Key Laboratory of Vascular Injury and Repair, Ningxia Medical 
      University, Yinchuan 750004, China.
FAU - Ma, Yan-Mei
AU  - Ma YM
AD  - School of Basic Medical Science, Ningxia Key Laboratory of Vascular Injury and 
      Repair, Ningxia Medical University, Yinchuan 750004, China.
FAU - Jing, Li
AU  - Jing L
AD  - School of Basic Medical Science, Ningxia Key Laboratory of Vascular Injury and 
      Repair, Ningxia Medical University, Yinchuan 750004, China.
FAU - Wang, Yi-Li
AU  - Wang YL
AD  - Institute For Cancer Research, School Of Basic Medical Science, Health Science 
      Center, Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: 
      wangyili@mail.xjtu.edu.cn.
FAU - Zhang, Jian-Zhong
AU  - Zhang JZ
AD  - School of Basic Medical Science, Ningxia Key Laboratory of Vascular Injury and 
      Repair, Ningxia Medical University, Yinchuan 750004, China.
LA  - eng
PT  - Journal Article
DEP - 20200409
PL  - Germany
TA  - Pathol Res Pract
JT  - Pathology, research and practice
JID - 7806109
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Hes1 protein, mouse)
RN  - 0 (Hes5 protein, mouse)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factor HES-1)
SB  - IM
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors/*metabolism
MH  - Cerebral Cortex/pathology/ultrastructure
MH  - Cognitive Dysfunction/*etiology/metabolism/pathology
MH  - Hyperhomocysteinemia/*complications/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurons/*pathology/ultrastructure
MH  - Repressor Proteins/*metabolism
MH  - Synapses/*pathology/ultrastructure
MH  - Transcription Factor HES-1/*metabolism
OTO - NOTNLM
OT  - Autophagy
OT  - Cognition
OT  - Hairy enhancer of split
OT  - Homocysteine
OT  - Synapse
OT  - Ultrastructure
COIS- Declaration of Competing Interest The authors declare that there are no conflicts 
      of interest.
EDAT- 2020/04/30 06:00
MHDA- 2021/04/02 06:00
CRDT- 2020/04/30 06:00
PHST- 2020/02/03 00:00 [received]
PHST- 2020/03/17 00:00 [revised]
PHST- 2020/03/29 00:00 [accepted]
PHST- 2020/04/30 06:00 [pubmed]
PHST- 2021/04/02 06:00 [medline]
PHST- 2020/04/30 06:00 [entrez]
AID - S0344-0338(20)30300-9 [pii]
AID - 10.1016/j.prp.2020.152953 [doi]
PST - ppublish
SO  - Pathol Res Pract. 2020 Jun;216(6):152953. doi: 10.1016/j.prp.2020.152953. Epub 
      2020 Apr 9.