Gestational diabetes exacerbates maternal immune activation effects in the developing brain

K. M. Money, T. L. Barke, A. Serezani, M. Gannon, K. A. Garbett, D. M. Aronoff, Karoly Mirnics

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalMolecular Psychiatry
Volume23
Issue number9
DOIs
StatePublished - Sep 1 2018

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Gestational Diabetes
Mothers
Brain
Psychiatry
Surrogate Mothers
Dopaminergic Neurons
Transcriptome
Chemokines
Innate Immunity
Epidemiologic Studies
Cytokines
Inflammation
Infection

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Gestational diabetes exacerbates maternal immune activation effects in the developing brain. / Money, K. M.; Barke, T. L.; Serezani, A.; Gannon, M.; Garbett, K. A.; Aronoff, D. M.; Mirnics, Karoly.

In: Molecular Psychiatry, Vol. 23, No. 9, 01.09.2018.

Research output: Contribution to journalArticle

Money, K. M. ; Barke, T. L. ; Serezani, A. ; Gannon, M. ; Garbett, K. A. ; Aronoff, D. M. ; Mirnics, Karoly. / Gestational diabetes exacerbates maternal immune activation effects in the developing brain. In: Molecular Psychiatry. 2018 ; Vol. 23, No. 9.
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