Tanaka Aki, Watanabe Yu, Kato Hiroyuki, Araki Tsutomu
Department of Drug Metabolism and Therapeutics, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, 1-78, Sho-machi, Tokushima 770-8505, Japan.
Mech Ageing Dev. 2007 Apr;128(4):303-10. doi: 10.1016/j.mad.2007.01.002. Epub 2007 Jan 21.
We investigated mainly immunohistochemical changes of nestin (a marker of neuroepithelial stem cells) and Ki-67 (a marker of proliferating cells) proteins related to ageing in the mouse hippocampus and subventricular zone (SVZ) using young adult (8 weeks old) and middle-aged (40 weeks old) mice. In the present study, no significant changes in neurons and astrocytes of the hippocampal CA1 sector were found in a middle-aged male ICR mice without severe senile weakness, as compared with young adult animals. In contrast, a significant change in the number of microglia was found in the hippocampal CA1 sector of the middle-aged mice. Furthermore, no significant changes in the number of nestin- and Ki-67-positive cells were observed in the hippocampal CA1 sector of the middle-aged mice. On the other hand, decreases in the number of nestin- and Ki-67-immunopositive cells were observed in the SVZ of the middle-aged mice. Furthermore, a migration of nestin- and Ki-67-immunoreactive cells in the corpus callosum was not observed in the SVZ of the middle-aged mice. In the dentate gyrus, significant decreases in the number of Ki-67-immunopositive cells were observed in the middle-aged mice. Our study also showed that nestin immunoreactivity was observed in both Ki-67-postive cells and astrocytes in the SVZ of young adult mice. These findings emphasize the need to recognize ageing as important factors in studies of microglia, which may help to clarify the role of glial cell structure and function during ageing processes. Furthermore, the present findings suggest that ageing processes may decrease neurogenesis in the corpus callosum, SVZ and dentate gyrus. Thus our present findings provide valuable information for the neurogenesis during ageing processes.
我们使用年轻成年(8周龄)和中年(40周龄)小鼠,研究了小鼠海马体和脑室下区(SVZ)中与衰老相关的巢蛋白(神经上皮干细胞标志物)和Ki-67(增殖细胞标志物)蛋白的主要免疫组化变化。在本研究中,与年轻成年动物相比,没有严重衰老虚弱的中年雄性ICR小鼠海马CA1区的神经元和星形胶质细胞没有显著变化。相反,在中年小鼠的海马CA1区发现小胶质细胞数量有显著变化。此外,在中年小鼠的海马CA1区未观察到巢蛋白和Ki-67阳性细胞数量的显著变化。另一方面,在中年小鼠的SVZ中观察到巢蛋白和Ki-67免疫阳性细胞数量减少。此外,在中年小鼠的SVZ中未观察到胼胝体中巢蛋白和Ki-67免疫反应性细胞的迁移。在齿状回中,中年小鼠中Ki-67免疫阳性细胞数量显著减少。我们的研究还表明,在年轻成年小鼠的SVZ中,在Ki-67阳性细胞和星形胶质细胞中均观察到巢蛋白免疫反应性。这些发现强调了在小胶质细胞研究中认识到衰老作为重要因素的必要性,这可能有助于阐明衰老过程中胶质细胞结构和功能的作用。此外,目前的发现表明,衰老过程可能会减少胼胝体、SVZ和齿状回中的神经发生。因此,我们目前的发现为衰老过程中的神经发生提供了有价值的信息。