Influence of catch up growth on spatial learning and memory in a mouse model of intrauterine growth restriction

<div><p>Background</p><p>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.</p><p>Methods</p><p>IUGR was induced by 50% maternal caloric undernutrition throughout late gestation. During the suckling period, dams were either fed <i>ad libitum</i> 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.</p><p>Results and conclusions</p><p>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.</p></div

Insulin metabolism.

<p><b>A</b>. Serum insulin levels were increased in NN and RN+ animals. Significant differences between groups *p < .05. <b>B.</b> Brain insulin receptor transcription was increased in RR and RN animals. <b>C.</b> Brain insulin receptor expression was increased in RR and NR animals. Significant differences compared to NN and NR+ *p < .05.</p

Graphical scheme of the experimental groups and procedures.

<p>A) <b>Animal model:</b> The diagram of the experiment is represented, with the different groups. B) <b>Functional evaluation:</b> The WMT is performed from 25 to 35 days. <b>C) Molecular tests:</b> Different test are performed for the molecular evaluation: Hormonal tests (ELISA), Protein quantification (Western blot) and RNA quantification (qPCR).</p

Pup growth evaluation.

<p>Pup weight two days after birth, by group. Pup weight at 21 days of life, by group.</p

BDNF and synaptic protein expression.

<p>A. BDNF mRNA expression was increased in the groups with better learning results. B. PSD95 and synaptophysin transcription. C. PSD95 and synaptophysin expression. There was a reduction in RR PSD95 expression. Significant differences compared to NN and NR+ *p < .05. No differences were observed in synaptophysin expression or trasncription.</p