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Genes Brain Behav ; 17(7): e12479, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29656594

RESUMO

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 upregulation 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 (IFN)-stimulated (gbp3, irgm1, ifi44), adolescent immunodevelopmental transcription factor (eg, r2, tfap2b), hormone (pomc, hcrt), adult selectin (sell, selp) and neuroligin (nlgn2) genes was altered. Systemic upregulation of endogenous IL-10 occurred at the adult stage, while both IL-1ß and IL-6 were increased and persisted in the sera throughout the growth of the MIA offspring. The cerebral IL-6 levels were endogenously upregulated, but both MCP-1 (macrophage inflammatory protein-1) and L-selectin levels were downregulated at the adolescent and/or adult stages. However, the MIA offspring were susceptible to lipopolysaccharide (LPS) stimulation. After reinjecting 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 phosphate-buffered saline (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.


Assuntos
Encéfalo/imunologia , Quimiocinas/imunologia , Citocinas/imunologia , Selectinas/imunologia , Transtornos do Comportamento Social/genética , Transtornos do Comportamento Social/imunologia , Fatores Etários , Animais , Comportamento Animal/fisiologia , Encéfalo/metabolismo , Quimiocinas/biossíntese , Quimiocinas/genética , Citocinas/biossíntese , Citocinas/genética , Modelos Animais de Doenças , Feminino , Expressão Gênica , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Selectinas/biossíntese , Selectinas/genética , Comportamento Social , Transcriptoma
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