PMID- 32777475
OWN - NLM
STAT- MEDLINE
DCOM- 20210915
LR  - 20211204
IS  - 1873-6823 (Electronic)
IS  - 0741-8329 (Linking)
VI  - 89
DP  - 2020 Dec
TI  - Prenatal alcohol exposure and maternal glutamine supplementation alter the mTOR 
      signaling pathway in ovine fetal cerebellum and skeletal muscle.
PG  - 93-102
LID - S0741-8329(20)30263-9 [pii]
LID - 10.1016/j.alcohol.2020.08.002 [doi]
AB  - Prenatal alcohol exposure causes fetal neurodevelopmental damage and growth 
      restriction. Among regions of the brain, the cerebellum is the most vulnerable to 
      developmental alcohol exposure. Despite vast research in the field, there is 
      still a need to identify specific mechanisms by which alcohol causes this damage 
      in order to design effective therapeutic interventions. The mammalian target of 
      rapamycin (mTOR) is known to be associated with axonal regeneration, dendritic 
      arborization, synaptic plasticity, cellular growth, autophagy, and many other 
      cellular processes. Glutamine and glutamine-related amino acids play a key role 
      in fetal development and are known to alter the mTOR pathway; recent research has 
      shown that disturbances in their bioavailability and signaling pathways may 
      mediate adverse effects of prenatal alcohol exposure. This study investigated the 
      role of the mTOR signaling pathway in the fetal cerebellum and skeletal muscle 
      after third trimester-equivalent prenatal alcohol exposure and maternal 
      l-glutamine (GLN) supplementation using a sheep model. Fetal cerebella and 
      skeletal muscles were sampled for Western blot analysis of mTOR and its 
      downstream targets S6 kinase and eukaryotic initiation factor 4E-bindin protein 
      (4E-BP1). The expression of cerebellar phosphorylated mTOR relative to the total 
      mTOR was elevated in the alcohol+GLN group compared to the saline and GLN groups. 
      Alcohol exposure increased the ratio of phosphorylated S6K to total S6K in fetal 
      cerebellum, and no significant effect of GLN supplementation was observed. On 
      contrary, maternal GLN supplementation reduced the activation of mTOR and S6K in 
      fetal skeletal muscle, possibly to make GLN and other amino acids available for 
      use by other organs. These findings suggest prenatal alcohol exposure and 
      maternal GLN supplementation during the third trimester-equivalent alter the mTOR 
      signaling cascade, which plays a possible key role in alcohol-induced 
      developmental damage.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Sawant, Onkar B
AU  - Sawant OB
AD  - Department of Veterinary Physiology and Pharmacology and Michael E. DeBakey 
      Institute, Texas A&M University, College Station, TX, 77843, United States.
FAU - Meng, Cong
AU  - Meng C
AD  - Department of Veterinary Physiology and Pharmacology and Michael E. DeBakey 
      Institute, Texas A&M University, College Station, TX, 77843, United States.
FAU - Wu, Guoyao
AU  - Wu G
AD  - Department of Animal Science, Texas A&M University, College Station, TX, 77843, 
      United States.
FAU - Washburn, Shannon E
AU  - Washburn SE
AD  - Department of Veterinary Physiology and Pharmacology and Michael E. DeBakey 
      Institute, Texas A&M University, College Station, TX, 77843, United States. 
      Electronic address: swashburn@cvm.tamu.edu.
LA  - eng
GR  - K08 AA018166/AA/NIAAA NIH HHS/United States
GR  - R01 AA010940/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200807
PL  - United States
TA  - Alcohol
JT  - Alcohol (Fayetteville, N.Y.)
JID - 8502311
RN  - 0RH81L854J (Glutamine)
RN  - 3K9958V90M (Ethanol)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cerebellum/*drug effects/metabolism
MH  - Dietary Supplements
MH  - Ethanol/*adverse effects
MH  - Female
MH  - *Glutamine/administration & dosage
MH  - Muscle, Skeletal/*drug effects/metabolism
MH  - Phosphorylation
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects/metabolism
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Sheep
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - alcohol
OT  - cerebellum
OT  - glutamine
OT  - mTOR
OT  - teratogenicity
EDAT- 2020/08/11 06:00
MHDA- 2021/09/16 06:00
CRDT- 2020/08/11 06:00
PHST- 2020/02/11 00:00 [received]
PHST- 2020/08/04 00:00 [revised]
PHST- 2020/08/04 00:00 [accepted]
PHST- 2020/08/11 06:00 [pubmed]
PHST- 2021/09/16 06:00 [medline]
PHST- 2020/08/11 06:00 [entrez]
AID - S0741-8329(20)30263-9 [pii]
AID - 10.1016/j.alcohol.2020.08.002 [doi]
PST - ppublish
SO  - Alcohol. 2020 Dec;89:93-102. doi: 10.1016/j.alcohol.2020.08.002. Epub 2020 Aug 7.