School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.
Department of Psychiatry, Monash University, Clayton, Victoria, Australia.
Hippocampus. 2021 Mar;31(3):321-334. doi: 10.1002/hipo.23291. Epub 2020 Dec 15.
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.
宫内生长受限 (IUGR) 与海马体改变有关，这些改变可能会增加日后短期记忆受损的风险。尽管海马体神经发生在学习和记忆中起着重要作用，但对 IUGR 对这些过程的长期影响的研究有限。我们旨在确定 IUGR 对青春期等效年龄时神经元增殖、分化和形态以及记忆功能的影响。在胚胎期第 18 天 (足月约在第 22 天) ，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)；通过假手术产生对照后代 (n=11)。从出生后第 36-44 天开始，进行自发位置识别 (SLR)、新物体位置和识别 (NOL、NOR) 以及旷场测试。在 P45 时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；Western blot 分析)。与对照组相比，IUGR 大鼠在 NOL 或 NOR 中的物体偏好、SLR 任务的相似和不同条件、旷场中的运动和焦虑样行为无差异。在 IUGR 大鼠的齿状回 (DG) 颗粒下区 (SGZ) 中，不成熟神经元 (DCX+) 的线性密度显著增加，但 SGZ 中增殖细胞 (Ki67+) 的线性密度、DG 中成熟神经元 (NeuN+) 或小胶质细胞 (Iba-1+) 的面积密度无差异。与对照组相比，两组之间齿状颗粒细胞的树突形态没有差异。与对照组相比，IUGR 大鼠海马体中 BDNF 前体 (pro-BDNF) 的蛋白表达增加，但成熟 BDNF 蛋白表达没有增加。这些发现强调了尽管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的海马体依赖性学习和记忆。
