Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model

Abstract

IntroductionIntrauterine growth restriction (IUGR) is the failure of the fetus to achieve its inherent growth potential, and it has frequently been associated with neurodevelopmental problems in childhood. Neurological disorders are mostly associated with IUGR babies with an abnormally high cephalization index (CI) and a brain sparing effect. However, a similar correlation has never been demonstrated in an animal model. The aim of this study was to determine the correlations between CI, functional deficits in learning and memory and alterations in synaptic proteins in a rat model of IUGR.MethodsUtero‐placental insufficiency was induced by meso‐ovarian vessel cauterization (CMO) in pregnant rats at embryonic day 17 (E17). Learning performance in an aquatic learning test was evaluated 25 days after birth and during 10 days. Some synaptic proteins were analyzed (PSD95, Synaptophysin) by Western blot and immunohistochemistry.ResultsPlacental insufficiency in CMO pups was associated with spatial memory deficits, which are correlated with a CI above the normal range. CMO pups presented altered levels of synaptic proteins PSD95 and synaptophysin in the hippocampus.ConclusionsThe results of this study suggest that learning disabilities may be associated with altered development of excitatory neurotransmission and synaptic plasticity. Although interspecific differences in fetal response to placental insufficiency should be taken into account, the translation of these data to humans suggest that both IUGR babies and babies with a normal birth weight but with intrauterine Doppler alterations and abnormal CI should be closely followed to detect neurodevelopmental alterations during the postnatal period.

Tadalafil treatment in mice for preeclampsia with fetal growth restriction has neuro-benefic effects in offspring through modulating prenatal hypoxic conditions

“…have recently shown WM microstructural alterations in children with ADHD using imaging data 21 . The dorsal hippocampus is associated with the cognitive functions that are impaired in ADHD children 22 . Rodent models of FGR exposed to hypoxia have shown that astrocyte accumulation and impaired myelination accompanies the WM injury after birth 23 .…”

Intrauterine Growth Restriction Causes Abnormal Embryonic Dentate Gyrus Neurogenesis in Mouse Offspring That Leads to Adult Learning and Memory Deficits

“…The hippocampus, a medial cortical structure required for forming new memories and learned behaviors ( Eichenbaum, 2000 ), is divided into the dentate gyrus (DG) and cornu ammonis (CA) fields in both humans and rodents, and is particularly susceptible to IUGR injury ( Gilchrist et al, 2018 ). Both children and animal models with IUGR have shown reductions in hippocampal volume by magnetic resonance imaging and correlated poorer memory performance ( Isaacs et al, 2000 ; Mallard et al, 2000 ; Lodygensky et al, 2008 ; Camprubí Camprubí et al, 2017 ). Multiple experimental models of IUGR have also indicated that both the neuron number and dendritic–axonal morphologies within the DG, CA1, and CA3 are altered following uteroplacental insufficiency.…”

Low Birth Weight Impairs Acquisition of Spatial Memory Task in Pigs

“…Impaired cognitive development associated with LBW has also been studied in a variety of animal models, most frequently in rats and sheep [although contrary to pigs and humans, LBW has to be experimentally induced in these models—( 8 )]. For example, LBW has been linked to spatial memory deficits in rats ( 9 ). Together, these findings suggest that LBW could have a long-term impact on cognitive functioning.…”