Format

Send to

Choose Destination
Brain Behav Immun. 2017 Oct;65:274-283. doi: 10.1016/j.bbi.2017.05.015. Epub 2017 May 22.

The role of IL-6 in neurodevelopment after prenatal stress.

Author information

1
Neuroscience Program, University of Iowa, 52242, United States; Child Study Center, Yale School of Medicine, 06510, United States.
2
Child Study Center, Yale School of Medicine, 06510, United States.
3
Neuroscience Program, University of Iowa, 52242, United States.
4
Neuroscience Program, University of Iowa, 52242, United States; Child Study Center, Yale School of Medicine, 06510, United States; Department of Psychiatry, University of Iowa Carver College of Medicine, 52242, United States. Electronic address: hanna-stevens@uiowa.edu.

Abstract

Prenatal stress exposure is associated with adverse psychiatric outcomes, including autism and ADHD, as well as locomotor and social inhibition and anxiety-like behaviors in animal offspring. Similarly, maternal immune activation also contributes to psychiatric risk and aberrant offspring behavior. The mechanisms underlying these outcomes are not clear. Offspring microglia and the pro-inflammatory cytokine interleukin-6 (IL-6), known to influence microglia, may serve as common mechanisms between prenatal stress and prenatal immune activation. To evaluate the role of prenatal IL-6 in prenatal stress, microglia morphological analyses were conducted at embryonic days 14 (E14), E15, and in adult mice. Offspring microglia and behavior were evaluated after repetitive maternal restraint stress, repetitive maternal IL-6, or maternal IL-6 blockade during stress from E12 onwards. At E14, novel changes in cortical plate embryonic microglia were documented-a greater density of the mutivacuolated morphology. This resulted from either prenatal stress or IL-6 exposure and was prevented by IL-6 blockade during prenatal stress. Prenatal stress also resulted in increased microglia ramification in adult brain, as has been previously shown. As with embryonic microglia, prenatal IL-6 recapitulated prenatal stress-induced changes in adult microglia. Furthermore, prenatal IL-6 was able to recapitulate the delay in GABAergic progenitor migration caused by prenatal stress. However, IL-6 mechanisms were not necessary for this delay, which persisted after prenatal stress despite IL-6 blockade. As we have previously demonstrated, behavioral effects of prenatal stress in offspring, including increased anxiety-like behavior, decreased sociability, and locomotor inhibition, may be related to these GABAergic delays. While adult microglia changes were ameliorated by IL-6 blockade, these behavioral changes were independent of IL-6 mechanisms, similar to GABAergic delays. This and previous work from our laboratory suggests that multiple mechanisms, including GABAergic delays, may underlie prenatal stress-linked deficits.

KEYWORDS:

Embryonic; Gaba; IL-6; Microglia; Prenatal stress

PMID:
28546058
PMCID:
PMC5537020
DOI:
10.1016/j.bbi.2017.05.015
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center