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Immune imbalance of global gene expression, and cytokine, chemokine and selectin levels in the brains of offspring with social deficits via maternal immune activation.

Immune imbalance of global gene expression, and cytokine, chemokine and selectin levels in the brains of offspring with social deficits via maternal immune activation.
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Hsueh PT, Lin HH, Wang HH, Liu CL, Ni WF, Liu JK, Chang HH, Sun DS, Chen YS, Chen YL,


Hsueh PT, Lin HH, Wang HH, Liu CL, Ni WF, Liu JK, Chang HH, Sun DS, Chen YS, Chen YL, (click to view)

Hsueh PT, Lin HH, Wang HH, Liu CL, Ni WF, Liu JK, Chang HH, Sun DS, Chen YS, Chen YL,

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Genes, brain, and behavior 2018 04 15() e12479 doi 10.1111/gbb.12479
Abstract

The murine maternal immune activation (MIA) offspring model enables longitudinal studies to explore aberrant social behaviors similar to those observed in humans. High levels of cytokines, chemokines and cell adhesion molecules (CAM) have been found in the plasma and/or brains of psychiatric patients. We hypothesized that up-regulation of the systemic or brain immune response has an augmenting effect by potentially increasing the interplay between the neuronal and immune systems during the growth of the MIA offspring. In this study, a C57BL/6j MIA female offspring model exhibiting social deficits was established. The expression of fetal interferon-stimulated (gbp3, irgm1, ifi44), adolescent immunodevelopmental transcription factor (egr2, tfap2b), hormone (pomc, hcrt), adult selectin (sell, selp) and neuroligin (nlgn2) genes was altered. Systemic up-regulation of endogenous IL-10 occurred at the adult stage, while both IL-1β and IL-6 were increased and persisted in the sera throughout the growth of the MIA offspring. The cerebral IL-6 levels were endogenously up-regulated, but both MCP-1 (macrophage inflammatory protein-1) and L-selectin levels were down-regulated at the adolescent and/or adult stages. However, the MIA offspring were susceptible to lipopolysaccharide (LPS) stimulation. After re-injecting the MIA offspring with LPS in adulthood, a variety of sera and cerebral cytokines, chemokines and CAMs were increased. Particularly, both MCP-1 and L-selectin showed relatively high expression in the brain compared with the expression levels in PBS-treated offspring injected with LPS. Potentially, MCP-1 was attracted to the L-selectin-mediated immune cells due to augmentation of the immune response following stimulation in MIA female offspring.

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