Hippocampal neurogenesis and memory in adolescence following intrauterine growth restriction

Abstract

Intrauterine growth restriction (IUGR) is associated with hippocampal alterations that can increase the risk of short‐term memory impairments later in life. Despite the role of hippocampal neurogenesis in learning and memory, research into the long‐lasting impact of IUGR on these processes is limited. We aimed to determine the effects of IUGR on neuronal proliferation, differentiation and morphology, and on memory function at adolescent equivalent age. At embryonic day (E) 18 (term ∼E22), placental insufficiency was induced in pregnant Wistar rats via bilateral uterine vessel ligation to generate IUGR offspring (n = 10); control offspring (n = 11) were generated via sham surgery. From postnatal day (P) 36–44, spontaneous location recognition (SLR), novel object location and recognition (NOL, NOR), and open field tests were performed. Brains were collected at P45 to assess neurogenesis (immunohistochemistry), dendritic morphology (Golgi staining), and brain‐derived neurotrophic factor expression (BDNF; Western blot analysis). In IUGR versus control rats there was no difference in object preference in the NOL or NOR, the similar and dissimilar condition of the SLR task, or in locomotion and anxiety‐like behavior in the open field. There was a significant increase in the linear density of immature neurons (DCX+) in the subgranular zone (SGZ) of the dentate gyrus (DG), but no difference in the linear density of proliferating cells (Ki67+) in the SGZ, nor in areal density of mature neurons (NeuN+) or microglia (Iba‐1+) in the DG in IUGR rats compared to controls. Dendritic morphology of dentate granule cells did not differ between groups. Protein expression of the BDNF precursor (pro‐BDNF), but not mature BDNF, was increased in the hippocampus of IUGR compared with control rats. These findings highlight that while the long‐lasting prenatal hypoxic environment may impact brain development, it may not impact hippocampal‐dependent learning and memory in adolescence.