Duran Fernandez-Feijoo Cristina, Carrasco Carrasco Cristina, Villalmazo Francisco Núria, Cebrià Romero Judit, Fernández Lorenzo Jose Ramon, Jiménez-Chillaron J C, Camprubí Camprubí Marta
Hospital Álvaro Cunqueiro, Pediatrics Service, Vigo, Spain.
Neonatology Service, BCNatal | Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Sant Joan de Déu and Hospital Clínic, University of Barcelona, Esplugues de Llobregat, Spain.
PLoS One. 2017 May 24;12(5):e0177468. doi: 10.1371/journal.pone.0177468. eCollection 2017.
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.
宫内生长受限（IUGR）以及出生后体重快速增加或追赶生长（CUG）会增加成年后患代谢综合征的易感性。纵向研究还显示，IUGR儿童学习困难的发生率很高。本研究的目的是在IUGR动物模型中研究营养和CUG对学习记忆的影响。我们假设，作为记忆巩固的重要机制，突触蛋白表达和转录可能会受到宫内营养不良的影响。
在整个妊娠后期，通过母体热量摄入减少50%诱导IUGR。在哺乳期，母鼠要么自由进食，要么限制饮食。幼崽被分为：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，通过水迷宫试验评估记忆。为了评估突触功能，通过蛋白质免疫印迹法和定量聚合酶链反应（qPCR）检测2种特定的突触蛋白（突触后致密蛋白95 [PSD95]、突触素）以及胰岛素受体（IR）。还研究了脑源性神经营养因子和血清胰岛素水平。
RN+组的学习曲线与NN组动物相似。无CUG的RR组动物存在学习障碍。RR组的PSD95低于NN组和RN+组小鼠。相比之下，所有组的突触素相似。IR的表达模式与PSD95相反。总之，围产期营养在学习中起重要作用。产前营养不良一段时间后的CUG似乎能改善学习技能。观察到的功能改变可能与PSD95活性降低以及突触可塑性激素调节可能出现的功能障碍有关。
