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成年小鼠两个品系齿状回神经发生的遗传影响。

Genetic influence on neurogenesis in the dentate gyrus of two strains of adult mice.

作者信息

Schauwecker Paula Elyse

机构信息

Department of Cell and Neurobiology, University of Southern California, Keck School of Medicine, 1333 San Pablo Street, BMT 403, Los Angeles, CA 90089-9112, USA.

出版信息

Brain Res. 2006 Nov 20;1120(1):83-92. doi: 10.1016/j.brainres.2006.08.086. Epub 2006 Sep 26.

DOI:10.1016/j.brainres.2006.08.086
PMID:16999941
Abstract

Previous studies have suggested that there is a genetic influence on the regulation of cell proliferation and survival within the hippocampus. However, the links between perturbations in neurogenesis and genomic control remain unclear. Here, we examined the impact of mouse strain on four parameters of the neurogenic program, proliferation, migration, differentiation and survival in the dentate gyrus of the hippocampus as a means of determining whether allelic variation of two independently derived mouse strains, FVB/NJ and C57BL/6J, modulates basal adult murine dentate gyrus neurogenesis. New cells were labeled with the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU) and their identity was determined immunocytochemically with various phenotypic markers. Consistent with previous studies in other strains of mice, we observed a strain-dependent difference in hippocampal proliferation. Hippocampal cell proliferation in FVB/NJ mice was reduced as compared to animals of the C57BL/6J strain. In contrast, the number of surviving cells in C57BL/6J mice was not significantly different from FVB/NJ mice. Regardless of mouse strain, the majority of surviving BrdU-labeled cells migrated into the granule cell layer and was of a neuronal phenotype. However, fewer surviving cells were located within the granule cell layer of FVB/NJ mice as compared to C57BL/6J mice. Overall, regardless of strain, no significant differences in the relative ratio of neurogenesis versus gliagenesis were observed. These results suggest that genetic background primarily influences newborn cell proliferation and migration, but not differentiation or survival.

摘要

先前的研究表明,基因对海马体内细胞增殖和存活的调节存在影响。然而,神经发生扰动与基因组控制之间的联系仍不明确。在此,我们研究了小鼠品系对神经发生程序的四个参数(增殖、迁移、分化和存活)的影响,这些参数位于海马齿状回中,以此来确定两个独立衍生的小鼠品系FVB/NJ和C57BL/6J的等位基因变异是否会调节成年小鼠齿状回的基础神经发生。用胸苷类似物5-溴-2'-脱氧尿苷(BrdU)标记新细胞,并通过各种表型标记物进行免疫细胞化学鉴定。与先前对其他小鼠品系的研究一致,我们观察到海马增殖存在品系依赖性差异。与C57BL/6J品系的动物相比,FVB/NJ小鼠的海马细胞增殖减少。相反,C57BL/6J小鼠中存活细胞的数量与FVB/NJ小鼠没有显著差异。无论小鼠品系如何,大多数存活的BrdU标记细胞迁移到颗粒细胞层,且具有神经元表型。然而,与C57BL/6J小鼠相比,FVB/NJ小鼠颗粒细胞层内的存活细胞较少。总体而言,无论品系如何,神经发生与胶质发生的相对比例均未观察到显著差异。这些结果表明,遗传背景主要影响新生细胞的增殖和迁移,但不影响分化或存活。

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