[1]宋莎菲,毛善平.SRPK2-TrkB分子相互调控在阿尔茨海默病模型小鼠中的作用[J].卒中与神经疾病杂志,2023,30(01):9-13.[doi:10.3969/j.issn.1007-0478.2023.01.002]
 Song Shafei,Mao Shanping..The role of SRPK and TrkB combination regulation in the Alzheimer's model[J].Stroke and Nervous Diseases,2023,30(01):9-13.[doi:10.3969/j.issn.1007-0478.2023.01.002]
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SRPK2-TrkB分子相互调控在阿尔茨海默病模型小鼠中的作用()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第30卷
期数:
2023年01期
页码:
9-13
栏目:
论著
出版日期:
2023-03-20

文章信息/Info

Title:
The role of SRPK and TrkB combination regulation in the Alzheimer's model
文章编号:
1007-0478(2023)01-0009-05
作者:
宋莎菲毛善平
430060 武汉大学人民医院神经内科[宋莎菲 毛善平(通信作者)]
Author(s):
Song Shafei Mao Shanping.
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060
关键词:
丝氨酸精氨酸蛋白激酶2 酪氨酸激酶受体B 阿尔茨海默病
Keywords:
SRPK2 TrkB AD
分类号:
R742
DOI:
10.3969/j.issn.1007-0478.2023.01.002
文献标志码:
A
摘要:
目的 探讨丝氨酸精氨酸蛋白激酶2(Serine/arginine-rich protein-specific kinase 2,SRPK2)在阿尔茨海默病(Alzheimer's disease,AD)模型小鼠中对酪氨酸激酶受体B(Tyrosine kinase receptor B,TrkB)的影响及作用。方法 将20只淀粉样前体蛋白(β-amyloid precursor protein,APP)/早老素1(Presenilin 1,PS1)/Tau蛋白(Tau protein,TAU)三转老鼠随机分为对照组(Green fluorescent protein,GFP组)(n=10)和实验组(SRPK2组)(n=10),利用向三转小鼠立体定位注射病毒,建立体外高表达SRPK2小鼠模型,于病毒注射28 d后通过新物体识别、水迷宫等行为学实验检测各组小鼠的认知功能,并以冰冻切片免疫荧光和免疫印迹等方法检测各组小鼠脑内TrkB、磷酸化TrkB,SRPK2、磷酸化SRPK2的蛋白表达水平。结果 与对照组(GFP组)比较,SRPK2组小鼠认知功能水平较GFP组升高(P<0.05); SRPK2组磷酸化TrkB表达水平降低,同时免疫荧光染色显示SRPK2组小鼠脑内磷酸化SRPK2的表达水平较GFP组升高。结论 Trk受体家族成员TrkB可能通过与SRPK2磷酸激酶相互作用来参与调节神经元功能,这可能是1个新的神经元功能调控位点。
Abstract:
ObjectiveTo explore the effect of SRPK2 kinase on TrkB receptor in Alzheimer's model mice.Methods Twenty APP/PS1/TAU three-transformed mice were randomly divided into a control group(GFP group)(n=10)and an experimental group(SRPK2 group)(n=10). The 3X TG mice were injected stereotaxically with virus to establish a mouse model with high expression of SRPK2 in vitro. The cognitive function of mice in each group by behaviors such as novel object recognition and water maze 28 days after virus injection were observed. And the brains of mice in each group were detected by frozen section immunofluorescence and western blotting. Subsequently, protein expression of TrkB, phosphorylated TrkB, SRPK2, and phosphorylated SRPK2 were detected.Results Compared with the control group(GFP group), the cognitive function level of the mice in the SRPK2 group was higher than that in the GFP group(P<0.05), the expression level of phosphorylated TrkB in the SRPK2 group was decreased, and immunofluorescence staining showed that the phosphorylation of the mice in the SRPK2 group was phosphorylated in the brain. The expression level of SRPK2 was higher than that in the GFP group.Conclusion Trk receptor family member TRKB can adjust the neuron function by interacting with SRPK2 phosphate,which may be a new neuron function regulation site.

参考文献/References:

[1] Alzheimer A, Stelzmann R, Schnitzlein, et al. An English translation of Alzheimer's 1907 paper, “Uber eine eigenartige Erkankung der Hirnrinde”[J]. Clinical anatomy(New York), 1995, 8(6): 429-431.
[2] Jin W. Regulation of BDNF-TrkB signaling and potential therapeutic strategies for Parkinson's disease[J]. J Clin Med, 2020, 9(1):257.
[3] Ferrer I, Mar n C, Rey MJ, et al. BDNF and full-length and truncated TrkB expression in Alzheimer disease.Implications in therapeutic strategies[J]. J Neuropathol Exp Neurol, 1999, 58(7): 729-739.
[4] Reichardt LF. Neurotrophin-regulated signalling pathways[J]. Philos Trans R Soc Lond B Biol Sci, 2006, 361(1473): 1545-1564.
[5] Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function[J]. Annu Rev Neurosci, 2001, 24(1): 677-736.
[6] Hamshere M, Holmans PA, Avramopoulos D, et al., Genome-wide linkage analysis of 723 affected relative pairs with late-onset Alzheimer's disease[J]. Hum Mol Genet, 2007, 16(22): 2703-2712.
[7] Ginsberg SD, Che S, Wuu J, et al. Down regulation of trk but not p75NTR gene expression in single cholinergic basal forebrain neurons mark the progression of Alzheimer's disease[J]. J Neurochem, 2006, 97(2): 475-487.
[8] Wang HY, Lin W, Dyck JA, et al. SRPK2:a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells[J]. J Cell Biol, 1998, 140(4): 737-750.
[9] Wang HY, Arden KC, Bermingham JJ, et al. Localization of serine kinases,SRPK1(SFRSK1)and SRPK2(SFRSK2),specific for the SR family of splicing factors in mouse and human chromosomes[J]. Genomics, 1999, 57(2): 310-315.
[10] Cunningham ME, Stephens RM, Kaplan DR, et al. Autophosphorylation of activation loop tyrosines regulates signaling by the TRK nerve growth factor receptor[J]. J Biol Chem, 1997, 272(16): 10957-10967.
[11] Huang YZ, McNamara JO. Mutual regulation of Src family kinases and the neurotrophin receptor TrkB[J]. J Biol Chem, 2010, 285(11): 8207-8217.
[12] 周源源.阿尔茨海默病的流行病学,发病危险因素,治疗及早期筛查研究进展[J].内科,2019,14(6):690-692.
[13] Guiton M, Gunn-Moore FJ, Stitt TN, et al. Identification of in vivo brain-derived neurotrophic factor-stimulated autophosphorylation sites on the TrkB receptor tyrosine kinase by site-directed mutagenesis[J]. Journal of Biological Chemistry, 1994, 269(48): 30370-30377.
[14] Aytan, Choi JK, Carreras I, et al. Protective effects of 7,8-dihydroxyflavone on neuropathological and neurochemical changes in a mouse model of Alzheimer's disease[J]. Eur J Pharmacol, 2018, 828(7): 9-17.
[15] Jang SW, Yang SJ, Ehlen A, et al. Serine/arginine protein-specific kinase 2 promotes leukemia cell proliferation by phosphorylating acinus and regulating cyclin A1[J]. Cancer Res,2008, 68(12): 4559-4570.
[16] Yang Y, Herrup K. Cell division in the CNS: protective response or lethal event in post-mitotic neurons[J]. Biochim Biophys Acta, 2007, 1772(4): 457-466.
[17] Schneider A. Phosphorylation that detaches tau protein from microtubules also protects it against aggregation into Alzheimer paired helical filaments[J].Biochemistry, 1999, 38(12): 3549-3558.
[18] Hong Y, Chan CB, Kwon IS, et al. SRPK2 phosphorylates tau and mediates the cognitive defects in Alzheimer's disease[J]. J Neurosci, 2012, 32(48): 17262-17272.
[19] Chan CB, Ye K. Serine-arginine protein kinases: new players in neurodegenerative diseases?[J]. Rev Neurosci, 2013, 24(4): 401-413.

更新日期/Last Update: 2023-03-20