Background: Babies born after intrauterine growth restriction (IUGR) are at increased risk of adverse long-term cognitive and memory deficits. Studies have found decreased neuronal numbers in the dentate gyrus of the hippocampus at birth and associated spatial memory deficits in adulthood in IUGR rats. We aimed to determine whether alterations to the hippocampus in utero following IUGR were still apparent in adolescence and if reduced hippocampal neurogenesis contributes to memory deficits later in life.
Methods: At day 18 of pregnancy (term=22 days), rats underwent bilateral uterine vessel ligation or sham surgery to generate IUGR (n=10) and control (n=11) pups. At postnatal day (P) 36 - 44 (adolescent equivalent-age), memory (Object Recognition and Object Location Memory) and pattern separation (similar and dissimilar Spontaneous Location Recognition) abilities were tested. Following testing at P45, brains were collected and processed for immunohistochemistry and western blot analysis. The dorsal hippocampus was assessed for the density of proliferating (Ki67-positive) and migrating cells (doublecortin [DCX]-positive), mature neurons (NeuN-positive), and protein expression of Brain Derived Neurotrophic Factor (BDNF) and its precursor (pro-BDNF). Data was assessed using a series of independent samples t-tests, and significance was set at p<0.05.
Results: In IUGR vs. control offspring there was an increase in i) the density of DCX-positive cells (p=0.017) and ii) pro-BDNF expression (p=0.036). However, no significant differences were observed in iii) memory performance, iv) pattern separation abilities, v) the density of Ki67- or NeuN- positive cells in the dorsal hippocampus, and vi) hippocampal BDNF expression.
Conclusions: While spatial memory performance is not affected in our study, an increase in cell migration and BDNF precursors in the hippocampus of IUGR adolescent rats may be maladaptive and requires further investigation.