Yang Zhongxi, Jun Heechul, Choi Chan-Ii, Yoo Ki Hyun, Cho Chang Hoon, Hussaini Syed Mohammed Qasim, Simmons Ambrosia J, Kim Seonhee, van Deursen Jan M, Baker Darren J, Jang Mi-Hyeon
Department of Neurologic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.
Department of Neurosurgery, First Hospital of Jilin University, Changchun, China.
Aging Cell. 2017 Jun;16(3):598-601. doi: 10.1111/acel.12594. Epub 2017 Apr 6.
Aging causes significant declines in adult hippocampal neurogenesis and leads to cognitive disability. Emerging evidence demonstrates that decline in the mitotic checkpoint kinase BubR1 level occurs with natural aging and induces progeroid features in both mice and children with mosaic variegated aneuploidy syndrome. Whether BubR1 contributes to age-related deficits in hippocampal neurogenesis is yet to be determined. Here we report that BubR1 expression is significantly reduced with natural aging in the mouse brain. Using established progeroid mice expressing low amounts of BubR1, we demonstrate these mice exhibit deficits in neural progenitor proliferation and maturation, leading to reduction in new neuron production. Collectively, our identification of BubR1 as a new and critical factor controlling sequential steps across neurogenesis raises the possibility that BubR1 may be a key mediator regulating aging-related hippocampal pathology. Targeting BubR1 may represent a novel therapeutic strategy for age-related cognitive deficits.
衰老导致成体海马神经发生显著下降，并引发认知障碍。新出现的证据表明，有丝分裂检查点激酶BubR1水平的下降与自然衰老有关，并在患有镶嵌杂合非整倍体综合征的小鼠和儿童中诱发早衰特征。BubR1是否导致与年龄相关的海马神经发生缺陷尚待确定。在此我们报告，在小鼠大脑中，BubR1的表达随自然衰老而显著降低。利用已建立的表达低水平BubR1的早衰小鼠，我们证明这些小鼠在神经祖细胞增殖和成熟方面存在缺陷，导致新神经元生成减少。总体而言，我们将BubR1鉴定为控制神经发生连续步骤的一个新的关键因素，这增加了BubR1可能是调节与衰老相关的海马病理的关键介质的可能性。靶向BubR1可能代表一种针对与年龄相关的认知缺陷的新型治疗策略。
