Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, Japan.
Reprod Toxicol. 2010 Dec;30(4):591-9. doi: 10.1016/j.reprotox.2010.08.009. Epub 2010 Oct 27.
Reelin signaling plays a role in neuronal migration and positioning during brain development. To clarify the effect of systemic growth retardation on the distribution of Reelin-expressing interneurons in the hilus of the hippocampal dentate gyrus, pregnant rats were fed a synthetic diet with either a normal (20% casein) or low (10% casein) protein concentration from gestational day 10 to postnatal day (PND) 21 at weaning. Male offspring were immunohistochemically examined at PND 21 and on PND 77. Protein-restricted offspring displayed systemic growth retardation through PND 77 and had decreased absolute brain weights and an increased number of external granular cells in the cerebellar cortex, suggestive of retarded brain growth at weaning. However, maternal protein restriction did not change the cellular distribution of immunoreactivity for Reelin, Calbindin-D-28K, or glutamic acid decarboxylase 67 or of NeuN-positive postmitotic neurons in the dentate hilus either at PND 21 or PND 77, which suggests that the population of γ-aminobutyric acid-ergic interneurons involving synthesis of Reelin was not affected. Furthermore, as well as the distribution of hilar neurons expressing neurogenesis-related FoxG1, cell proliferation and apoptosis in the subgranular zone were unaffected through PND 77. These results suggest that systemic growth retardation caused by maternal protein restriction does not affect neuronal migration and postnatal neurogenesis of the dentate gyrus resulting in unaltered distribution of Reelin-synthesizing interneurons.
Reelin 信号在大脑发育过程中神经元迁移和定位中发挥作用。为了阐明系统性生长迟缓对海马齿状回门区 Reelin 表达中间神经元分布的影响,从妊娠第 10 天到断奶后第 21 天(PND),给怀孕的大鼠喂食含有正常(20%酪蛋白)或低(10%酪蛋白)蛋白浓度的合成饮食。雄性后代在 PND 21 和 PND 77 时进行免疫组织化学检查。限制蛋白饮食的后代通过 PND 77 表现出系统性生长迟缓,并且小脑皮质中的外颗粒细胞绝对数量减少,表明断奶时大脑生长迟缓。然而,母体蛋白限制并没有改变 PND 21 或 PND 77 时 Reelin、Calbindin-D-28K 或谷氨酸脱羧酶 67 的免疫反应性细胞分布,也没有改变齿状回门区 NeuN 阳性有丝分裂后神经元的分布,这表明涉及 Reelin 合成的 γ-氨基丁酸能中间神经元群体没有受到影响。此外,在 PND 77 时,表达神经发生相关 FoxG1 的门区神经元的分布以及颗粒下区的细胞增殖和细胞凋亡均不受影响。这些结果表明,母体蛋白限制引起的系统性生长迟缓不会影响齿状回的神经元迁移和出生后神经发生,从而导致 Reelin 合成中间神经元的分布不变。