DDX3和酪蛋白激酶1ε在肌萎缩侧索硬化症转基因鼠海马中的表达

doi:10.16098/j.issn.0529-1356.2017.04.002

解剖学报 ›› 2017, Vol. 48 ›› Issue (4): 375-380.doi: 10.16098/j.issn.0529-1356.2017.04.002

DDX3和酪蛋白激酶1ε在肌萎缩侧索硬化症转基因鼠海马中的表达

蒲蕾东¹ 张雅雯¹王箐² 刘焕彩³刘永新¹王巧真² 管英俊¹ 陈燕春^1*

1.潍坊医学院组织学与胚胎学教研室; 2.人体解剖学教研室; 3.附属医院骨科，山东潍坊 261053

收稿日期:2016-09-19 修回日期:2016-10-24 出版日期:2017-08-06 发布日期:2017-08-06
通讯作者: 陈燕春 E-mail:cyc7907@163.com
基金资助:
国家自然科学基金;国家自然科学基金;山东省自然科学基金;山东省自然科学基金;山东省科技发展计划项目;山东省教育厅课题;山东省教育厅课题

Expression of DDX3 and casein kinase 1ε in the hippocampus of the amyotrophic lateral sclerosis transgenic mice

PU Lei-dong¹ZHANG Ya-wen¹ WANG Qing²LIU Huan-cai³LIU Yong-xin¹WANG Qiao-zhen² GUAN Ying-jun¹ CHEN Yan-chun^1*

1. Department of Histology and Embryology; 2. Department of Human Anatomy; 3. Department of Orthopaedics, Affiliated Hospital, Weifang Medical University, Shandong Weifang 261053,China

Received:2016-09-19 Revised:2016-10-24 Online:2017-08-06 Published:2017-08-06
Contact: CHEN Yan-chun E-mail:cyc7907@163.com

摘要/Abstract

摘要：

目的检测DDX3和酪蛋白激酶1ε(CK1ε)在肌萎缩侧索硬化症(ALS)转基因鼠海马中的表达变化，揭示DDX3和CK1ε的表达改变与ALS发病的关系。方法 33只ALS转基因鼠和33只野生型鼠分别于发病不同时期取材，应用RT-PCR和Western blotting技术检测海马组织中DDX3和CK1ε的表达变化；通过免疫荧光双标染色技术观察DDX3和CK1ε阳性细胞的分布特点及其与神经元、星形胶质细胞等的共表达情况。结果与野生型鼠相比，ALS转基因鼠海马中DDX3 mRNA和蛋白在发病早期变化不明显，中期和晚期表达均明显降低；CK1ε mRNA和蛋白则在发病早期、中期和晚期表达均降低。免疫荧光双标结果显示，在ALS鼠和野生型鼠海马齿状回区和CA区均可检测到DDX3和CK1ε阳性细胞。DDX3和CK1ε主要表达在神经元，在星形胶质细胞未见表达。与野生型鼠比较，ALS转基因鼠海马中DDX3和CK1ε免疫反应性明显降低。结论 DDX3和CK1ε mRNA和蛋白在ALS转基因鼠海马中表达均降低，表明DDX3和CK1ε表达异常与ALS海马区病变密切相关。

关键词: 肌萎缩侧索硬化症, 海马, DDX3, 酪蛋白激酶1ε, 转基因, 免疫印迹法, 小鼠

Abstract:

Objective To detect the expression of DDX3 and casein kinase 1ε(CK1ε) in the hippocampus of the amyotrophic lateral sclerosis (ALS) transgenic mice, and to explore the relationship between the expression of DDX3 or CK1ε and the pathogenesis of ALS. Methods Thirty-three wild ALS transgenic mice and thirty-three wild-type mice were killed at different stages. The expressions of DDX3 and CK1ε were detected by RT-PCR and Western blotting. The distribution of DDX3 and CK1ε positive cells in the hippocampus and the coexpression of DDX3 or CK1ε with astrocytes or neurons in the hippocampus were detected by a double immunofluorescence technology. Results DDX3 mRNA and protein in the hippocampus of ALS mice were of no significant differences at the early stage, but decreased at the middle and end stages, compared with wild-type mice. CK1ε mRNA and protein were all decreased at the three different stages, compared with the wild-type mice. Double immunofluorescence result showed that DDX3 and CK1ε positive cells were co-localized in the district demtate gyrusc(DG) and CA of the hippocampus. DDX3 and CK1ε mainly expressed in neurons, not in astrocytes. Compared with the wild-type mice, the immunoreactivity of DDX3 and CK1ε in the hippocampus of ALS mice decreased obviously. Conclusion The expression of both DDX3 and CK1ε mRNA and protein decrease in the hippocampus of ALS mice, compared with the wild-type mice, indicating that the abnormal expression of DDX3 and CK1ε is closely related to hippocampus lesion in ALS.

Key words: Amyotrophic lateral sclerosis, Hippocampus, DDX3, Casein kinase 1ε, Transgenic, Western blotting, Mouse

蒲蕾东张雅雯王箐刘焕彩刘永新王巧真管英俊陈燕春. DDX3和酪蛋白激酶1ε在肌萎缩侧索硬化症转基因鼠海马中的表达[J]. 解剖学报, 2017, 48(4): 375-380.

PU Lei-dong ZHANG Ya-wen WANG Qing LIU Huan-cai LIU Yong-xin WANG Qiao-zhen GUAN Ying-jun CHEN Yan-chun. Expression of DDX3 and casein kinase 1ε in the hippocampus of the amyotrophic lateral sclerosis transgenic mice[J]. Acta Anatomica Sinica, 2017, 48(4): 375-380.

参考文献

[1] Paez-Colasante X, FigueroaRomero C, Sakowski SA, et al. Amyotrophic lateral sclerosis: mechanisms and therapeutics in the epigenomic era［J］. Nat Rev Neurol,2015,11(5):266-279.

［2］Abdulla S, Machts J, Kaufmann J, et al. Hippocampal degeneration in patients with amyotrophic lateral sclerosis［J］.Neurobiol Aging, 2014, 35(11):2339-2345.

［3］Cruciat CM, Dolde C, de Groot RE, et al. RNA helicase DDX3 is a regulatory subunit of casein kinase 1 in Wnt-β-catenin signaling［J］. Science, 2013, 339(6126):1436-1441.

［4］Chen Y, Guan Y, Liu H,et al. Activation of the Wnt/β-catenin signaling pathway is associated with glial proliferation in the adult spinal cord of ALS transgenic mice［J］. Biochem Biophys Res Commun,2012, 420 (2): 397-403.

［5］Chen Y, Guan Y, Zhang Z,et al. Wnt signaling pathway is involved in the pathogenesis of amyotrophic lateral sclerosis in adult transgenic mice［J］.Neurol Res, 2012，34(4):390-399.

［6］Zhang CX, Guan YJ, Chen YCh,et al. The expression of Wnt5a in the dentate gyrus of ALS transgenic mice［J］.Acta Academiae Medicineae Weifang,2013,35(2):81-83. (in Chinese)

张彩霞,管英俊,陈燕春,等. Wnt5a在ALS转基因鼠海马齿状回中的表达变化［J］. 潍坊医学院学报, 2013,35(2):81-83.

［7］Wang ShSh, Chen YCh, Guan YJ, et al. Expression change of the secreted frizzled-related protein 4 in spinal cord of amyotrophic lateral sclerosis transgenic mice［J］. Acta Anatomica Sinica, 2012, 43(4):439-444.(in Chinese)

王珊珊，陈燕春，管英俊，等.sFRP4在ALS转基因鼠脊髓中的表达变化［J］.解剖学报, 2012,43(4):439-444.

［8］Cui LY, Kang DX,Zhang Ch, et al. Summary of the Eleventh International Symposium on amyotrophic lateral sclerosis /motor neuron disease［J］. Chinese Journal of Neurology, 2001, 34(3):182-183. (in Chinese)

崔丽英, 康德暄, 张成, 等. 第十一届国际肌萎缩侧索硬化症/运动神经元病专题研讨会纪要［J］.中华神经科杂志, 2001, 34(3):182-183.

［9］Kawashima T, Doh-Ura K, Kikuchi H,et al. Cognitive dysfunction in patients with amyotrophic lateral sclerosis is associated with spherical or crescent-shaped ubiquitinated intraneuronal inclusions in the parahippocampal gyrus and amygdala, but not in the neostriatum［J］.Acta Neuropathol,2001, 102(5):467-472.

［10] Quarta E,Bravi R,Scambi I, et al. Increased anxiety-like behavior and selective learning impairments are concomitant to loss of hippocampal interneurons in the presymptomatic SOD1(G93A) ALS mouse model［J］. J Comp Neurol, 2015, 523(11):1622-1638.

［11］Abdulla S,Machts J,Kaufmann J,et al. Hippocampal degeneration in patients with amyotrophic lateral sclerosis ［J］. Neurobiol Aging, 2014, 35(11):2639-2645.

［12］Yokota O, Terada S, Ishizu H, et al. Increased expression of neuronal cyclooxygenase-2 in the hippocampus in amyotrophic lateral sclerosis both with and without dementia［J］. Acta Neuropathol, 2004, 107(5):399-405.

［13］Thielsen KD, Moser JM, Schmitt-John T, et al. The Wobbler mouse model of amyotrophic lateral sclerosis (ALS) displays hippocampal hyperexcitability, and reduced number of interneurons, but no presynaptic vesicle release impairments［J］.PLoS One,2013,8(12):e82767.

［14］Bol GM, Vesuna F, Xie M, et al. Targeting DDX3 with a small molecule inhibitor for lung cancer therapy［J］.EMBO Mol Med,2015,7(5):648-669.

［15］Bischof J, Müller A, Fnder M, et al. Neurite outgrowth of mature retinal ganglion cells and PC12 cells requires activity of CK1δ and CK1ε［J］. PLoS One, 2011, 6(6):e20857.

［16］Flajolet M, He G, Heiman M, et al. Regulation of Alzheimer’s disease amyloid-beta formation by casein kinase I［J］. Proc Natl Acad Sci USA, 2007, 104(10):4159-4164.

［17］Polakis P. Casein Kinase 1: a Wnt’er of disconnect［J］. Curr Biol, 2002, 12(14): 499-501.

［18］Farías GG, Godoy JA, Cerpa W, et al. Wnt signaling modulates pre-and postsynaptic maturation:therapeutic considerations［J］.Dev Dyn,2010, 239(1):94-101.

［19］Yim DG, Virshup DM.Unwinding the Wnt action of casein kinase 1［J］. Cell Res, 2013, 23(6):737-738.

［20］He TY, Wu DW, Lin PL, et al. DDX3 promotes tumor invasion in colorectal cancer via the CK1ε/Dvl2 axis［J］. Sci Rep, 2016,19(6):e21483.

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DDX3和酪蛋白激酶1ε在肌萎缩侧索硬化症转基因鼠海马中的表达

Expression of DDX3 and casein kinase 1ε in the hippocampus of the amyotrophic lateral sclerosis transgenic mice

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