Department of Integrative Traditional & Western Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China.
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea.
Neural Regen Res. 2014 Oct 1;9(19):1731-9. doi: 10.4103/1673-5374.143415.
Long-term administration of scopolamine, a muscarinic receptor antagonist, can inhibit the survival of newly generated cells, but its effect on the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus remain poorly understood. In this study, we used immunohistochemistry and western blot methods to weekly detect the biological behaviors of nerve cells in the hippocampal dentate gyrus of adult mice that received intraperitoneal administration of scopolamine for 4 weeks. Expression of neuronal nuclear antigen (NeuN; a neuronal marker) and Fluoro-Jade B (a marker for the localization of neuronal degeneration) was also detected. After scopolamine treatment, mouse hippocampal neurons did not die, and Ki-67 (a marker for proliferating cells)-immunoreactive cells were reduced in number and reached the lowest level at 4 weeks. Doublecortin (DCX; a marker for newly generated neurons)-immunoreactive cells were gradually shortened in length and reduced in number with time. After scopolamine treatment for 4 weeks, nearly all of the 5-bromo-2'-deoxyuridine (BrdU)-labeled newly generated cells were located in the subgranular zone of the dentate gyrus, but they did not migrate into the granule cell layer. Few mature BrdU/NeuN double-labeled cells were seen in the subgranular zone of the dentate gyrus. These findings suggest that long-term administration of scopolamine interferes with the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus, but it does not induce cell death.
长期给予毒蕈碱受体拮抗剂东莨菪碱可抑制新生细胞的存活,但它对成年小鼠海马齿状回神经细胞的增殖、分化和迁移的影响仍知之甚少。在这项研究中,我们使用免疫组织化学和 Western blot 方法,每周检测腹腔给予东莨菪碱 4 周的成年小鼠海马齿状回神经细胞的生物学行为。还检测了神经元核抗原(NeuN;神经元标志物)和氟硼酸(一种神经元变性定位标志物)的表达。东莨菪碱处理后,小鼠海马神经元未死亡,Ki-67(增殖细胞标志物)免疫反应性细胞数量减少,在第 4 周达到最低水平。双皮质素(DCX;新生神经元标志物)免疫反应性细胞的长度逐渐缩短,数量随时间减少。东莨菪碱处理 4 周后,几乎所有的 5-溴-2'-脱氧尿苷(BrdU)标记的新生细胞都位于齿状回的颗粒下区,但它们没有迁移到颗粒细胞层。在齿状回的颗粒下区很少见到成熟的 BrdU/NeuN 双标记细胞。这些发现表明,长期给予东莨菪碱会干扰成年小鼠海马齿状回神经细胞的增殖、分化和迁移,但不会诱导细胞死亡。