Influence of catch up growth on spatial learning and memory in a mouse model of intrauterine growth restriction.
Influence of catch up growth on spatial learning and memory in a mouse model of intrauterine growth restriction.
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DOI：
10.1371/journal.pone.0177468
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Camprubí Camprubí M
中科院分区：
文献类型：
--
作者：
Duran Fernandez-Feijoo C;Carrasco Carrasco C;Villalmazo Francisco N;Cebrià Romero J;Fernández Lorenzo JR;Jiménez-Chillaron JC;Camprubí Camprubí M
宫内生长受限（IUGR）和出生后体重快速增加或追赶性生长（CUG）增加了成年期代谢综合征的易感性。纵向研究也揭示了IUGR儿童学习困难的高发病率。本研究的目的是探讨营养和CUG对IUGR动物模型学习记忆的影响。我们假设突触蛋白表达和转录（记忆巩固的重要机制）可能会受到宫内营养不良的影响。在整个妊娠晚期，50%的母体热量营养不良诱导IUGR。在哺乳期间，母鼠可自由进食或限制进食。幼仔分为：正常产前饮食-正常产后饮食（NN）、限制产前饮食-正常产后饮食+追赶生长（RN+）、正常产前饮食-限制产后饮食（NR）和限制产前饮食-限制产后饮食（RR）。在4周龄时，通过水迷宫测试评估记忆。为了评价突触功能，通过蛋白质印迹和定量聚合酶链反应（qPCR）检测了2种特异性突触蛋白（突触后密度-95 [PSD 95]，突触素）以及胰岛素受体（IR）。脑源性神经营养因子和血清胰岛素水平也进行了研究。RN+组呈现出与NN动物相似的学习曲线。没有CUG的RR动物表现出学习障碍。RR组的PSD 95低于NN和RN+小鼠。相反，突触素在所有组中相似。IR显示与PSD 95相反的表达模式。总之，围产期营养在学习中起着重要作用。经过一段时间的产前营养不良CUG似乎提高学习技能。所观察到的功能改变可能与较低的PSD 95活性和突触可塑性的激素调节中可能的功能障碍有关。
Intrauterine growth restriction (IUGR) and rapid postnatal weight gain or catch up growth (CUG) increase the susceptibility to metabolic syndrome during adult life. Longitudinal studies have also revealed a high incidence of learning difficulties in children with IUGR. The aim of the present study was to investigate the effect of nutrition and CUG on learning memory in an IUGR animal model. We hypothesized that synaptic protein expression and transcription, an essential mechanism for memory consolidation, might be affected by intrauterine undernutrition. IUGR was induced by 50% maternal caloric undernutrition throughout late gestation. During the suckling period, dams were either fed ad libitum or food restricted. The pups were divided into: Normal prenatal diet-Normal postnatal diet (NN), Restricted prenatal diet- Normal postnatal diet + catch up growth (RN+), Normal prenatal diet-Restricted postnatal diet (NR) and Restricted prenatal diet-Restricted postnatal diet (RR). At 4 weeks of age, memory was assessed via a water maze test. To evaluate synaptic function, 2 specific synaptic proteins (postsynaptic density-95 [PSD95], synaptophysin) as well as insulin receptors (IR) were tested by Western Blot and quantitative polymerase chain reaction (qPCR). Brain-derived neurotrophic factor and serum insulin levels were also studied. The RN+ group presented a learning curve similar to the NN animals. The RR animals without CUG showed learning disabilities. PSD95 was lower in the RR group than in the NN and RN+ mice. In contrast, synaptophysin was similar in all groups. IR showed an inverse expression pattern to that of the PSD95. In conclusion, perinatal nutrition plays an important role in learning. CUG after a period of prenatal malnutrition seems to improve learning skills. The functional alterations observed might be related to lower PSD95 activity and a possible dysfunction in the hormone regulation of synaptic plasticity.