Developing Brain Glucose Transporters, Serotonin, Serotonin Transporter, and Oxytocin Receptor Expression in Response to Early-Life Hypocaloric and Hypercaloric Dietary, and Air Pollutant Exposures.
Developing Brain Glucose Transporters, Serotonin, Serotonin Transporter, and Oxytocin Receptor Expression in Response to Early-Life Hypocaloric and Hypercaloric Dietary, and Air Pollutant Exposures.
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脑葡萄糖转运蛋白，5-羟色胺，5-羟色胺转运蛋白和催产素受体的表达，响应早期生命的低温和过度饮食以及空气污染物的暴露。
DOI：
10.1159/000514709
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发表时间：
2021
影响因子：
2.9
通讯作者：
Devaskar SU
中科院分区：
文献类型：
--
作者：
Ye X;Shin BC;Baldauf C;Ganguly A;Ghosh S;Devaskar SU
母体饮食紊乱和产前暴露于空气污染会影响胎儿大脑，易导致产后神经行为障碍。葡萄糖转运蛋白（GLUT）在为神经传递提供能量方面至关重要，神经元亚型GLUT3的缺乏最终会导致自闭症谱系障碍。与不同的神经递质一样，血清素（5 - HT）和催产素（OXT）对神经连接的发育至关重要。血清素转运体（SERT）调节突触的5 - HT水平，而催产素受体（OXTR）介导催产素的作用。我们假设受干扰的脑GLUT1/GLUT3调节的5 - HT - SERT失衡是产后神经精神表型的一个促成因素，而OXT/OXTR起到平衡作用。采用母体饮食限制（宫内生长受限，IUGR）、高脂肪（HF）饮食调整以及产前暴露于模拟空气污染（AP）的方法，通过酶联免疫吸附测定（ELISA）评估胎儿（胚胎第19天）小鼠大脑的5 - HT，通过免疫组织化学对SERT和OXTR进行定位，并通过定量蛋白质印迹分析进行测量。与年龄和性别匹配的对照组相比，头部重量较低的宫内生长受限导致雄性和雌性胎儿大脑GLUT3减少48%，GLUT1无变化，OXTR无显著变化。此外，胎儿宫内生长受限大脑中5 - HT和SERT浓度降低约50%（p = 0.005）。相比之下，尽管出现小头畸形，但母体高脂肪饮食或空气污染暴露并未引起显著变化。我们得出结论，在胎儿大脑发育过程中的宫内生长受限情况下，GLUT3减少与5 - HT - SERT轴失衡有关。我们推测这些早期变化可能为改变5HT - SERT神经轴以及产后相关神经发育障碍的出现奠定基础。
Perturbed maternal diet and prenatal exposure to air pollution affects the fetal brain, predisposing to postnatal neurobehavioral disorders. Glucose transporters (GLUT) are key in fueling neurotransmission, deficiency of the neuronal isoform GLUT3 culminates in autism spectrum disorders. Along with the different neurotransmitters, serotonin (5-HT) and oxytocin (OXT) are critical for the development of neural connectivity. Serotonin transporter (SERT) modulates synaptic 5-HT levels, while OXT receptor (OXTR) mediates OXT action. We hypothesized that perturbed brain GLUT1/GLUT3 regulated 5-HT-SERT imbalance, serves as a contributing factor to postnatal neuropsychiatric phenotypes, with OXT/OXTR providing a counterbalance. Employing maternal diet restricted (IUGR), high fat (HF) dietary modifications, and prenatal exposure to simulated air pollution (AP), fetal (E19) murine brain 5-HT was assessed by ELISA with SERT and OXTR being localized by immunohistochemistry, and measured by quantitative Western blot analysis. IUGR with lower head weights led to a 48% reduction in male and female fetal brain GLUT3 with no change in GLUT1, when compared to age- and sex-matched controls, with no significant change in OXTR. In addition, a ~50% (p=0.005) decrease in 5-HT and SERT concentrations was displayed in fetal IUGR brains. In contrast, despite emergence of microcephaly, exposure to a maternal high fat diet or air pollution caused no significant changes. We conclude that in the IUGR during fetal brain development, reduced GLUT3 is associated with an imbalanced 5-HT-SERT axis. We speculate that these early changes may set the stage for altering the 5HT-SERT neural axis with postnatal emergence of associated neurodevelopmental disorders.
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影响因子：
10
作者：
Chang YC;Cole TB;Costa LG
通讯作者：
Costa LG
影响因子：
13.5
作者：
Daws, Lynette C.;Gould, Georgianna G.
通讯作者：
Gould, Georgianna G.
影响因子：
4.3
作者：
Edlow, Andrea G.;Guedj, Faycal;Bianchi, Diana W.
通讯作者：
Bianchi, Diana W.
影响因子：
4.1
作者：
Dobolyi, A.;Kekesi, K. A.;Kovacs, Z.
通讯作者：
Kovacs, Z.
影响因子：
6.1
作者：
Chauhan, V;Breznan, D;Vincent, R
通讯作者：
Vincent, R