PMID- 32333505
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20211204
IS  - 1932-846X (Electronic)
IS  - 1932-8451 (Linking)
VI  - 80
IP  - 5-6
DP  - 2020 May
TI  - The effect of intrauterine inflammation on mTOR signaling in mouse fetal brain.
PG  - 149-159
LID - 10.1002/dneu.22755 [doi]
AB  - Fetuses exposed to an inflammatory environment are predisposed to long-term 
      adverse neurological outcomes. However, the mechanism by which intrauterine 
      inflammation (IUI) is responsible for abnormal fetal brain development is not 
      fully understood. The mechanistic target of rapamycin (mTOR) signaling pathway is 
      closely associated with fetal brain development. We hypothesized that mTOR 
      signaling might be involved in fetal brain injury and malformation when fetuses 
      are exposed to the IUI environment. A well-established IUI model was utilized by 
      intrauterine injection of lipopolysaccharide (LPS) to explore the effect of IUI 
      on mTOR signaling in mouse fetal brains. We found that microglia activation in 
      LPS fetal brains was increased, as demonstrated by elevated Iba-1 protein level 
      and immunofluorescence density. LPS fetal brains also showed reduced neuronal 
      cell counts, decreased cell proliferation demonstrated by low Ki67-positive 
      density, and elevated neuron apoptosis evidenced by high expression of cleaved 
      Caspase 3. Furthermore, we found that mTOR signaling in LPS fetal brains was 
      elevated at 2 hr after LPS treatment, declined at 6 hr and showed overall 
      inhibition at 24 hr. In summary, our study revealed that LPS-induced IUI leads to 
      increased activation of microglia cells, neuronal damage, and dynamic alterations 
      in mTOR signaling in the mouse fetal brain. Our findings indicate that abnormal 
      changes in mTOR signaling may underlie the development of future neurological 
      complications in offspring exposed to prenatal IUI.
CI  - (c) 2020 Wiley Periodicals LLC.
FAU - Dong, Jie
AU  - Dong J
AUID- ORCID: 0000-0001-6786-1057
AD  - Department of Gynecology and Obstetrics, Integrated Research Center for Fetal 
      Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
AD  - Department of Obstetrics and Gynecology, Reproductive Medical Center, Tangdu 
      Hospital, Air Force Medical University, Xi'an, China.
FAU - Lei, Jun
AU  - Lei J
AD  - Department of Gynecology and Obstetrics, Integrated Research Center for Fetal 
      Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
FAU - Elsayed, Nada A
AU  - Elsayed NA
AUID- ORCID: 0000-0003-3641-2114
AD  - Department of Gynecology and Obstetrics, Integrated Research Center for Fetal 
      Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
FAU - Lee, Ji Yeon
AU  - Lee JY
AD  - Department of Gynecology and Obstetrics, Integrated Research Center for Fetal 
      Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
FAU - Shin, Na
AU  - Shin N
AD  - Department of Gynecology and Obstetrics, Integrated Research Center for Fetal 
      Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
FAU - Na, Quan
AU  - Na Q
AD  - Department of Gynecology and Obstetrics, Integrated Research Center for Fetal 
      Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
FAU - Chudnovets, Anna
AU  - Chudnovets A
AD  - Department of Gynecology and Obstetrics, Integrated Research Center for Fetal 
      Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
FAU - Jia, Bei
AU  - Jia B
AD  - Department of Gynecology and Obstetrics, Integrated Research Center for Fetal 
      Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
FAU - Wang, Xiaohong
AU  - Wang X
AD  - Department of Obstetrics and Gynecology, Reproductive Medical Center, Tangdu 
      Hospital, Air Force Medical University, Xi'an, China.
FAU - Burd, Irina
AU  - Burd I
AD  - Department of Gynecology and Obstetrics, Integrated Research Center for Fetal 
      Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
LA  - eng
GR  - Johns Hopkins Integrated Research Center for Fetal Medicine Fund/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200603
PL  - United States
TA  - Dev Neurobiol
JT  - Developmental neurobiology
JID - 101300215
RN  - 0 (Lipopolysaccharides)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - *Brain Diseases/immunology/metabolism/pathology
MH  - *Cerebral Cortex/immunology/metabolism/pathology
MH  - Disease Models, Animal
MH  - Female
MH  - Fetal Development/immunology/*physiology
MH  - *Fetal Diseases/immunology/metabolism/pathology
MH  - *Inflammation/immunology/metabolism/pathology
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - *Microglia/immunology/metabolism
MH  - Pregnancy
MH  - Signal Transduction/immunology/*physiology
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - fetal neurodevelopment
OT  - intrauterine inflammation
OT  - mTOR signaling
EDAT- 2020/04/26 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/04/26 06:00
PHST- 2019/09/09 00:00 [received]
PHST- 2019/10/24 00:00 [revised]
PHST- 2020/04/20 00:00 [accepted]
PHST- 2020/04/26 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/04/26 06:00 [entrez]
AID - 10.1002/dneu.22755 [doi]
PST - ppublish
SO  - Dev Neurobiol. 2020 May;80(5-6):149-159. doi: 10.1002/dneu.22755. Epub 2020 Jun 
      3.