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.

中文翻译：

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宫内生长受限后青春期的海马神经发生和记忆

宫内生长受限 (IUGR) 与海马体的改变有关，这会增加以后生活中短期记忆障碍的风险。尽管海马神经发生在学习和记忆中的作用，但对 IUGR 对这些过程的长期影响的研究是有限的。我们的目的是确定 IUGR 对神经元增殖、分化和形态以及对青春期同等年龄记忆功能的影响。在胚胎第 (E) 18 天 (term ∼E22)，通过双侧子宫血管结扎在怀孕的 Wistar 大鼠中诱导胎盘功能不全，以产生 IUGR 后代 ( n = 10)；控制后代 ( n =11）是通过假手术产生的。从出生后第 36-44 天 (P) 开始，进行自发位置识别 (SLR)、新物体定位和识别 (NOL、NOR) 以及野外测试。在 P45 收集大脑以评估神经发生（免疫组织化学）、树突形态（高尔基染色）和脑源性神经营养因子表达（BDNF；蛋白质印迹分析）。在 IUGR 与对照大鼠中，NOL 或 NOR 的对象偏好、SLR 任务的相似和不同条件、或开放场中的运动和焦虑样行为没有差异。齿状回（DG）颗粒下区（SGZ）未成熟神经元（DCX+）的线密度显着增加，但SGZ中增殖细胞（Ki67+）的线密度无差异，与对照组相比，IUGR 大鼠 DG 中成熟神经元 (NeuN+) 或小胶质细胞 (Iba-1+) 的面积密度也不相同。齿状颗粒细胞的树突形态在各组之间没有差异。与对照大鼠相比，IUGR 的海马中 BDNF 前体 (pro-BDNF) 的蛋白质表达增加，而不是成熟的 BDNF。这些发现强调，虽然长期的产前低氧环境可能会影响大脑发育，但它可能不会影响青春期依赖海马的学习和记忆。