PMID- 34555455
OWN - NLM
STAT- MEDLINE
DCOM- 20211123
LR  - 20220531
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 176
DP  - 2021 Nov 20
TI  - Expanding role of vitamin E in protection against metabolic dysregulation: 
      Insights gained from model systems, especially the developing nervous system of 
      zebrafish embryos.
PG  - 80-91
LID - S0891-5849(21)00729-2 [pii]
LID - 10.1016/j.freeradbiomed.2021.09.016 [doi]
AB  - This review discusses why the embryo requires vitamin E (VitE) and shows that its 
      lack causes metabolic dysregulation and impacts morphological changes at very 
      early stages in development, which occur prior to when a woman knows she is 
      pregnant. VitE halts the chain reactions of lipid peroxidation (LPO). Metabolomic 
      analyses indicate that thiols become depleted in E- embryos because LPO generates 
      products that require compensation using limited amino acids and methyl donors 
      that are also developmentally relevant. Thus, VitE protects metabolic networks 
      and the integrated gene expression networks that control development. VitE is 
      critical especially for neurodevelopment, which is dependent on trafficking by 
      the alpha-tocopherol transfer protein (TTPa). VitE-deficient (E-) zebrafish embryos 
      initially appear normal, but by 12 and 24 h post-fertilization (hpf) E- embryos 
      are developmentally abnormal with expression of pax2a and sox10 mis-localized in 
      the midbrain-hindbrain boundary, neural crest cells and throughout the spinal 
      neurons. These patterning defects indicate cells that are especially in need of 
      VitE-protection. They precede obvious morphological abnormalities (cranial-facial 
      malformation, pericardial edema, yolksac edema, skewed body-axis) and impaired 
      behavioral responses to locomotor activity tests. The TTPA gene (ttpa) is 
      expressed at the leading edges of the brain ventricle border. Ttpa knockdown 
      using morpholinos is 100% lethal by 24 hpf, while E- embryo brains are often 
      over- or under-inflated at 24 hpf. Further, E- embryos prior to 24 hpf have 
      increased expression of genes involved in glycolysis and the pentose phosphate 
      pathway, and decreased expression of genes involved in anabolic pathways and 
      transcription. Combined data from both gene expression and the metabolome in E- 
      embryos at 24 hpf suggest that the activity of the mechanistic Target of 
      Rapamycin (mTOR) signaling pathway is decreased, which may impact both metabolism 
      and neurodevelopment. Further evaluation of VitE deficiency in neurogenesis and 
      its subsequent impact on learning and behavior is needed.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Head, Brian
AU  - Head B
AD  - Linus Pauling Institute, Corvallis, OR, USA; Molecular and Cell Biology Program, 
      Corvallis, OR, USA.
FAU - Traber, Maret G
AU  - Traber MG
AD  - Linus Pauling Institute, Corvallis, OR, USA; School of Biological and Population 
      Health Sciences, College of Public Health and Human Sciences, Oregon State 
      University, Corvallis, OR, USA. Electronic address: maret.traber@oregonstate.edu.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210920
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 1406-18-4 (Vitamin E)
SB  - IM
MH  - Animals
MH  - Embryo, Nonmammalian
MH  - Female
MH  - Humans
MH  - Lipid Peroxidation
MH  - Models, Animal
MH  - Nervous System
MH  - Pregnancy
MH  - *Vitamin E
MH  - *Zebrafish/genetics
OTO - NOTNLM
OT  - Ataxia with vitamin E deficiency (AVED)
OT  - Betaine
OT  - Choline
OT  - Embryogenesis
OT  - Glutathione
OT  - Lipid peroxidation
OT  - Neurogenesis
OT  - Zebrafish
OT  - alpha-tocopherol
OT  - alpha-tocopherol transfer protein
EDAT- 2021/09/24 06:00
MHDA- 2021/11/24 06:00
CRDT- 2021/09/23 20:13
PHST- 2021/05/27 00:00 [received]
PHST- 2021/07/27 00:00 [revised]
PHST- 2021/09/07 00:00 [accepted]
PHST- 2021/09/24 06:00 [pubmed]
PHST- 2021/11/24 06:00 [medline]
PHST- 2021/09/23 20:13 [entrez]
AID - S0891-5849(21)00729-2 [pii]
AID - 10.1016/j.freeradbiomed.2021.09.016 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2021 Nov 20;176:80-91. doi: 
      10.1016/j.freeradbiomed.2021.09.016. Epub 2021 Sep 20.