期刊
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
卷 53, 期 -, 页码 18-25出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ijdevneu.2016.06.005
关键词
Developmental programming; Arcuate nucleus; Neurodevelopment; pSTAT3; Inflammation
资金
- New Zealand Lottery Health Grant
- University of Otago Department of Anatomy doctoral scholarship
Maternal obesity during pregnancy is associated with chronic maternal, placental, and fetal inflammation; and it elevates the risk for offspring obesity. Changes in the development of the hypothalamus, a brain region that regulates body weight and energy balance, are emerging as important determinants of offspring risk, but such changes are only beginning to be defined. Here we focused on the hypothesis that the pathological exposure of developing hypothalamic astrocytes to cytokines would alter their development. A maternal high-fat diet (mHFD) mouse model was used to investigate changes in hypothalamic astrocytes in the fetus during late gestation and in early neonates by using immunochemistry, confocal microscopy, and qPCR. The number of astrocytes and the proportion of proliferating astrocytes was significantly higher in the arcuate nucleus (ARC) and the supraoptic nucleus (SON) of the hypothalamus at both ages compared to control offspring from normal weight pregnancies. Supplemental to this we found that cultured fetal hypothalamic astrocytes proliferated significantly in response to IL6 (10 ng/ml), one of the cytokines significantly elevated in fetuses of obese dams, via the JAK/STAT3 signaling pathway. Thus, maternal obesity during pregnancy stimulated the proliferation and thereby increased numbers of astrocytes in the fetal as well as early neonatal hypothalamus, which may be driven, during fetal life, by IL6. (C) 2016 ISDN. Published by Elsevier Ltd. All rights reserved.
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