PMID- 31217051
OWN - NLM
STAT- MEDLINE
DCOM- 20190808
LR  - 20211204
IS  - 2214-0190 (Electronic)
IS  - 0895-3988 (Linking)
VI  - 32
IP  - 5
DP  - 2019 May
TI  - Persistently Upregulated Hippocampal mTOR Signals Mediated by Fecal SCFAs Impair 
      Memory in Male Pups with SMM Exposure in Utero.
PG  - 345-356
LID - 10.3967/bes2019.046 [doi]
AB  - OBJECTIVE: To investigate the molecular mechanisms of the adverse effects of 
      exposure to sulfamonomethoxin (SMM) in pregnancy on the neurobehavioral 
      development of male offspring. METHODS: Pregnant mice were randomly divided into 
      four groups: control- (normal saline), low- [10 mg/(kg*day)], middle- [50 
      mg/(kg*day)], and high-dose [200 mg/(kg*day)] groups, which received SMM by 
      gavage daily during gestational days 1-18. We measured the levels of short-chain 
      fatty acids (SCFAs) in feces from dams and male pups. Furthermore, we analyzed 
      the mRNA and protein levels of genes involved in the mammalian target of 
      rapamycin (mTOR) pathway in the hippocampus of male pups by RT-PCR or Western 
      blotting. RESULTS: Fecal SCFA concentrations were significantly decreased in 
      dams. Moreover, the production of individual fecal SCFAs was unbalanced, with a 
      tendency for an increased level of total fecal SCFAs in male pups on postnatal 
      day (PND) 22 and 56. Furthermore, the phosphatidylinositol 3-kinase 
      (PI3k)/protein kinase B (AKT)/mTOR or mTOR/ribosomal protein S6 kinase 1 
      (S6K1)/4EBP1 signaling pathway was continuously upregulated until PND 56 in male 
      offspring. In addition, the expression of Sepiapterin Reductase (SPR), a 
      potential target of mTOR, was inhibited. CONCLUSION: In utero exposure to SMM, 
      persistent upregulation of the hippocampal mTOR pathway related to dysfunction of 
      the gut (SCFA)-brain axis may contribute to cognitive deficits in male offspring.
CI  - Copyright (c) 2019 The Editorial Board of Biomedical and Environmental Sciences. 
      Published by China CDC. All rights reserved.
FAU - Zhu, Yi Tian
AU  - Zhu YT
AD  - Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical 
      University, Hefei 230032, Anhui, China.
FAU - Liu, Xin Ji
AU  - Liu XJ
AD  - Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical 
      University, Hefei 230032, Anhui, China.
FAU - Liu, Kai Yong
AU  - Liu KY
AD  - Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical 
      University, Hefei 230032, Anhui, China; Anhui Provincial Key Laboratory of 
      Population Health and Aristogenics, Hefei 230032, Anhui, China.
FAU - Zhang, Qiang
AU  - Zhang Q
AD  - Hefei Municipal Center for Disease Control and Prevention, Hefei 230000, Anhui, 
      China.
FAU - Yang, Lin Sheng
AU  - Yang LS
AD  - Department of Epidemiology and Biostatistics, School of Public Health, Anhui 
      Medical University, Hefei 230032, Anhui, China.
FAU - Wei, Rong
AU  - Wei R
AD  - Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical 
      University, Hefei 230032, Anhui, China.
FAU - Zhang, Jing Jing
AU  - Zhang JJ
AD  - Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical 
      University, Hefei 230032, Anhui, China.
FAU - Tao, Fang Biao
AU  - Tao FB
AD  - Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei 
      230032, Anhui, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Biomed Environ Sci
JT  - Biomedical and environmental sciences : BES
JID - 8909524
RN  - 0 (Anti-Infective Agents)
RN  - 0 (Fatty Acids, Volatile)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.1.153 (sepiapterin reductase)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - U700P169W2 (Sulfamonomethoxine)
MH  - Alcohol Oxidoreductases/metabolism
MH  - Animals
MH  - Anti-Infective Agents/*toxicity
MH  - Fatty Acids, Volatile/analysis
MH  - Feces/chemistry
MH  - Female
MH  - Hippocampus/*drug effects/metabolism
MH  - Male
MH  - Memory/*drug effects
MH  - Mice, Inbred ICR
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Sulfamonomethoxine/*toxicity
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - Cognitive deficits
OT  - Mammalian target of rapamycin
OT  - Sepiapterin reductase
OT  - Short-chain fatty acids
OT  - Sulfamonomethoxine
EDAT- 2019/06/21 06:00
MHDA- 2019/08/09 06:00
CRDT- 2019/06/21 06:00
PHST- 2018/10/30 00:00 [received]
PHST- 2019/05/08 00:00 [accepted]
PHST- 2019/06/21 06:00 [entrez]
PHST- 2019/06/21 06:00 [pubmed]
PHST- 2019/08/09 06:00 [medline]
AID - 10.3967/bes2019.046 [doi]
PST - ppublish
SO  - Biomed Environ Sci. 2019 May;32(5):345-356. doi: 10.3967/bes2019.046.