PMID- 28948973
OWN - NLM
STAT- MEDLINE
DCOM- 20190731
LR  - 20220716
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 23
IP  - 9
DP  - 2018 Sep
TI  - Gestational diabetes exacerbates maternal immune activation effects in the 
      developing brain.
PG  - 1920-1928
LID - 10.1038/mp.2017.191 [doi]
AB  - Maternal inflammation and diabetes increase the risk for psychiatric disorders in 
      offspring. We hypothesized that these co-occurring risk factors may potentiate 
      each other. To test this, we maternally exposed developing mice in utero to 
      gestational diabetes mellitus (GDM) and/or maternal immune activation (MIA). 
      Fetal mouse brains were exposed to either vehicle, GDM, MIA or GDM+MIA. At 
      gestational day (GD) 12.5, GDM produced a hyperglycemic, hyperleptinemic maternal 
      state, whereas MIA produced significant increases in proinflammatory cytokines 
      and chemokines. Each condition alone resulted in an altered, inflammatory and 
      neurodevelopmental transcriptome profile. In addition, GDM+MIA heightened the 
      maternal inflammatory state and gave rise to a new, specific transcriptional 
      response. This exacerbated response was associated with pathways implicated in 
      psychiatric disorders, including dopamine neuron differentiation and innate 
      immune response. Based on these data, we hypothesize that children born to GDM 
      mothers and exposed to midgestation infections have an increased vulnerability to 
      psychiatric disorder later in life, and this should be tested in follow-up 
      epidemiological studies.
FAU - Money, K M
AU  - Money KM
AD  - Neuroscience Graduate Program, Vanderbilt University, Nashville, TN, USA.
AD  - Vanderbilt Medical Scientist Training Program, Vanderbilt University, Nashville, 
      TN, USA.
FAU - Barke, T L
AU  - Barke TL
AD  - Graduate Program in Microbiology and Immunology, Vanderbilt University, 
      Nashville, TN, USA.
AD  - Division of Infectious Diseases, Department of Medicine, Vanderbilt University 
      Medical Center, Nashville, TN, USA.
FAU - Serezani, A
AU  - Serezani A
AD  - Division of Allergy, Department of Medicine, Pulmonary and Critical Care, 
      Vanderbilt University Medical Center, Nashville, TN, USA.
FAU - Gannon, M
AU  - Gannon M
AD  - Division of Diabetes, Department of Medicine, Endocrinology and Metabolism, 
      Vanderbilt University Medical Center, Nashville, TN, USA.
FAU - Garbett, K A
AU  - Garbett KA
AD  - Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
FAU - Aronoff, D M
AU  - Aronoff DM
AD  - Division of Infectious Diseases, Department of Medicine, Vanderbilt University 
      Medical Center, Nashville, TN, USA.
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University 
      Medical Center, Nashville, TN, USA.
FAU - Mirnics, K
AU  - Mirnics K
AD  - Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska 
      Medical Center, Omaha, NE, USA. karoly.mirnics@unmc.edu.
LA  - eng
GR  - F31 DK108652/DK/NIDDK NIH HHS/United States
GR  - R01 MH079299/MH/NIMH NIH HHS/United States
GR  - T32 GM007347/GM/NIGMS NIH HHS/United States
GR  - T32 MH064913/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170926
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
MH  - Animals
MH  - Brain/drug effects/embryology
MH  - Chemokines/metabolism
MH  - Cytokines/metabolism
MH  - Diabetes, Gestational/*immunology/*physiopathology
MH  - Female
MH  - Immunity, Active/*immunology/physiology
MH  - Inflammation/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mothers
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/physiopathology
MH  - Risk Factors
PMC - PMC6459194
MID - NIHMS976744
EDAT- 2017/09/28 06:00
MHDA- 2019/08/01 06:00
PMCR- 2019/04/11
CRDT- 2017/09/27 06:00
PHST- 2017/02/27 00:00 [received]
PHST- 2017/07/13 00:00 [accepted]
PHST- 2017/07/04 00:00 [revised]
PHST- 2017/09/28 06:00 [pubmed]
PHST- 2019/08/01 06:00 [medline]
PHST- 2017/09/27 06:00 [entrez]
PHST- 2019/04/11 00:00 [pmc-release]
AID - 10.1038/mp.2017.191 [pii]
AID - 10.1038/mp.2017.191 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2018 Sep;23(9):1920-1928. doi: 10.1038/mp.2017.191. Epub 2017 Sep 
      26.