Objective To observe the changes of cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus of APP/PS1 double transgenic Alzheimer's disease mice, and investigate the effects of Tiaoxin formula on learning and memory.Methods Totally, 54 three-month-old APP/PS1 transgenic mice were randomly divided into model group (n=18), positive control (donepezil) group (n=18) and Tiaoxin formula group (n=18). Another 18 three-month-old C57/BL6 wild mice were chosen as normal group with same strain and same age. All administration groups received relevant medicine. Twelve weeks later, Morris water maze test was used to test the behavior. The real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of CREB mRNA and BDNF mRNA in hippocampus. Western blotting was used to detect the expression of phosphorylated CREB (p-CREB) and BDNF in hippocampus.Results Compared with the model group, the escape latency significantly shortened (P<0.01), the percentage of staying time in the quadrant of original platform significantly increased (P<0.05), the expression of CREB mRNA and BDNF mRNA in hippocampus significantly increased (P<0.05), and the expression of p-CREB and BDNF protein in hippocampus significantly increased (P<0.01) in Tiaoxin formula group.Conclusion Tiaoxin formula could improve the spatial learning and memory of APP/PS1 double transgenic mice with AD, which might be related to the up-regulation of CREB/BDNF signaling pathway.
WANG Xiao-wen
,
DENG Hai-yan
,
WANG Jian
,
XU Ying
. Role of cAMP Response Element Binding Protein/Brain-derived Neurotrophic Factor Signaling Pathway in Tiaoxin Formula Improving Learning and Memory of APP/PS1 Mice[J]. Chinese Journal of Rehabilitation Theory and Practice, 2018
, 24(1)
: 11
-16
.
DOI: 10.3969/j.issn.1006-9771.2018.01.003
[1] Trittschuh EH, Crane PK, Larson EB, et al. Effects of varying diagnostic criteria on prevalence of mild cognitive impairment in a community based sample [J]. J Alzheimers Dis, 2011,25(1): 163-173.
[2] Mattsson N, Schott JM, Hardy J, et al. Selective vulnerability in neurodegeneration: insights from clinical variants of Alzheimer's disease [J]. J Neurol Neurosurg Psychiatry, 2016, 87(9): 1000-1004.
[3] Bauckneht M, Picco A, Nobili F, et al. Amyloid positron emission tomography and cognitive reserve [J]. World J Radiol, 2015, 7(12): 475-483.
[4] 岳姣姣. 盐酸多奈哌齐在阿尔茨海默病治疗中的应用研究[J]. 中国医药指南, 2017, 15(15): 49-50.
[5] 王健,林水森,周如倩,等. 调心方治疗Alzheimer病的临床研究[J]. 北京中医药大学学报, 2002, 25(3): 51-53.
[6] 胡志红,闫君宝,杨东伟. 游泳训练次数对大鼠Morris水迷宫成绩的影响[J]. 山西医科大学学报, 2016, 47(1): 18-21.
[7] 闫盼盼,闫国立,詹向红,等. Morris 水迷宫实验设计的统计学方法探析[J]. 中华中医药学刊, 2013, 31(2): 264-266.
[8] Singh S, Kaur H, Sandhir R. Fractal dimensions: A new paradigm to assess spatial memory and learning using Morris water maze [J]. Behav Brain Res, 2016, 15(299): 141-146.
[9] 武海霞,吴志刚,刘红滨,等. Morris 水迷宫实验在空间学习记忆研究中的应用[J]. 神经药理学报, 2014, 4(5): 30-35.
[10] Fischer W, Bjorklund A, Chen K, et al. NGF improves spatial memory in aged rodents as a function of age [J]. J Neurosci, 1991, 11(7): 1889-1906.
[11] 王怀颖,石少慧. 环腺苷酸应答元件结合蛋白与学习记忆[J]. 生命的化学, 2008, 28(4): 453-455.
[12] 何萍,陈家欢,黄晓亮,等. 慢性吗啡处理对大鼠交感神经节pCREB和CREB mRNA表达的影响[J]. 中国药理学通报, 2013, 29(2): 238-241.
[13] Takemori H, Kajimura J, Okamoto M. TORC-SIK cascade regulates CREB activity through the basic leucine zipper domain [J]. FEBS J, 2007(13): 3202-3209.
[14] Li YF, Cheng YF, Huang Y, et al. Phosphodiesterase-4D knock-out and RNA interference-mediated knock-down enhance memory and increase hippocampal neurogenesis via increased cAMP signaling [J]. J Neurosci, 2011, 31(1): 172-183.
[15] 黄效东,杨新华,卢永辉. 白藜芦醇通过抑制CREB 磷酸化减轻癫痫发作并改善认知功能[J]. 实用医学杂志, 2017, 33(1): 72-75.
[16] 余汇,陈佳佳,曾冰倩,等. cAMP/CREB/BDNF信号通路在沃替西汀抗小鼠抑郁样行为中的作用[J]. 南方医科大学学报, 2017, 37(1): 107-112.
[17] Zhu DY, Lau L, Liu SH, et al. Activation of cAMP-response-element-binding protein (CREB) after focal cerebral ischemia stimulates neurogenesis in the adult dentate gyrus [J]. Proc Natl Acad Sci USA, 2004, 101(25): 9453- 9457.
[18] Deisseroth K, Bito H, Tsien RW. Signaling from synapse to nucleus: postsynaptic CREB phosphorylation during multiple forms of hippocampal synaptic plasticity [J]. Neuron, 1996, 16(1): 89-101.
[19] Hinoi E, Balcar VJ, Kuramoto N, et al. Nuclear transcription factors in the hippocampus [J]. Prog Neurobiol, 2002, 68(2): 145-165.
[20] Niu L, Zhou J, Huang Y, et al. db-Cyclic adenosine monophosphate promotes axon regeneration and motor function recovery in cerebral ischemia-reperfusion rats [J]. Neurol India, 2010, 58(2): 195-200.
[21] Aid T, Kazantseva A, Piirsoo M, et al. Mouse and rat BDNF gene structure and expression revisited [J]. J Neurosci Res, 2007, 85(3): 525-535.
[22] Leyhe T, Eschweiler GW, Stransky E, et al. Increase of BDNF serum concentration in lithium treated patients with early Alzheimer's disease [J]. J Alzheimers Dis, 2009, 16(3): 649-656.
[23] Mlyniec K, Budziszewska B, Holst BA, et al. GPR39 (Zinc receptor) knockout mice exhibit depression-like behavior and CREB/BDNF Down Regulation in the hippocampus [J]. Int J Neuropsychopharmacol, 2014, 18(3) pii: pyu002.
[24] Ge L, Liu L, Liu S, et al. Resveratrol abrogates lipopolysaccharide-induced depressive-like behavior, neuroinflammatory response, and CREB/BDNF signaling in mice [J]. Eur J Pharmacol, 2015, 5(768): 49-57.
[25] Ji Y, Pang PT, Feng L, et al. Cyclic AMP controls BDNF-induced TrkB phosphorylation and dendritic spine formation in mature hippocampal neurons [J]. Nat Neurosci, 2005, 8(2): 164-172.
[26] 彭生,杨建平,张晓庆,等. 磷酸二酯酶-4抑制剂Ro20-1724对氯胺酮麻醉后学习记忆及大鼠海马cAMP-PKA-CREB- BDNF信号通路的影响[J]. 中华行为医学与脑科学杂志, 2014, 23(6): 528-530.
