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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

氟西汀可预防中年APPswe / PSEN1dE9双转基因阿尔茨海默氏病小鼠的树突棘损失

卷 17, 期 1, 2020

页: [93 - 103] 页: 11

弟呕挨: 10.2174/1567205017666200213095419

价格: $65

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摘要

背景：研究表明，阿尔茨海默氏病（AD）的认知障碍与树突棘丧失有关，尤其是在海马中。氟西汀（FLX）已被证明可以改善AD早期的认知，并与减少海马突触变性有关。然而，关于FLX是否在中晚期阶段影响AD的发病机理以及其作用是否与海马树突功能障碍的改善相关，人们所知甚少。以前，已经观察到FLX可以改善中年APP / PS1小鼠的空间学习能力。 目的：在本研究中，我们进一步表征了FLX对中年APP / PS1小鼠海马树突棘的影响。 结果：已经发现，FLX显着增加了海马齿状回（DG），CA1和CA2 / 3的树突棘数量。同时，FLX有效减弱了Ser396上tau的过度磷酸化，并提高了海马突触后密度95（PSD-95）和突触蛋白1（SYN-1）的蛋白水平。 结论：这些结果表明，FLX治疗的中年APP / PS1小鼠观察到的学习能力增强可能与FLX显着减轻海马树突状脊柱病理有关，并暗示FLX有望被探索为治疗AD的新策略在中后期。

关键词: 氟西汀，树突棘，海马，学习能力，阿尔茨海默氏病，神经退行性疾病。

« Previous Next »
[1]
Selkoe DJ. Alzheimer’s disease is a synaptic failure. Science 298(5594): 789-91. (2002).
[http://dx.doi.org/10.1126/science.1074069] [PMID: 12399581]
[2]
Boros BD, Greathouse KM, Gentry EG, Curtis KA, Birchall EL, Gearing M, et al. Dendritic spines provide cognitive resilience against Alzheimer’s disease. Ann Neurol 82(4): 602-14. (2017).
[http://dx.doi.org/10.1002/ana.25049] [PMID: 28921611]
[3]
Terry RD, Masliah E, Salmon DP, DeTeresa R, Hill R, Hansen LA, et al. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30(4): 572-80. (1991).
[http://dx.doi.org/10.1002/ana.410300410] [PMID: 1789684]
[4]
Carlisle HJ, Kennedy MB. Spine architecture and synaptic plasticity. Trends Neurosci 28(4): 182-7. (2005).
[http://dx.doi.org/10.1016/j.tins.2005.01.008] [PMID: 15808352]
[5]
Fortin DA, Srivastava T, Soderling TR. Structural modulation of dendritic spines during synaptic plasticity. Neuroscientist 18(4): 326-41. (2012).
[http://dx.doi.org/10.1177/1073858411407206] [PMID: 21670426]
[6]
Parajuli LK, Tanaka S, Okabe S. Insights into age-old questions of new dendritic spines: From form to function. Brain Res Bull 129: 3-11. (2017).
[http://dx.doi.org/10.1016/j.brainresbull.2016.07.014] [PMID: 27491624]
[7]
Dorostkar MM, Zou C, Blazquez-Llorca L, Herms J. Analyzing dendritic spine pathology in Alzheimer’s disease: problems and opportunities. Acta Neuropathol 130(1): 1-19. (2015).
[http://dx.doi.org/10.1007/s00401-015-1449-5] [PMID: 26063233]
[8]
Penzes P, Cahill ME, Jones KA, VanLeeuwen JE, Woolfrey KM. Dendritic spine pathology in neuropsychiatric disorders. Nat Neurosci 14(3): 285-93. (2011).
[http://dx.doi.org/10.1038/nn.2741] [PMID: 21346746]
[9]
Wong DT, Perry KW, Bymaster FP. Case history: the discovery of fluoxetine hydrochloride (Prozac). Nat Rev Drug Discov 4(9): 764-74. (2005).
[http://dx.doi.org/10.1038/nrd1821] [PMID: 16121130]
[10]
Mowla A, Mosavinasab M, Pani A. Does fluoxetine have any effect on the cognition of patients with mild cognitive impairment? A double-blind, placebo-controlled, clinical trial. J Clin Psychopharmacol 27(1): 67-70. (2007).
[http://dx.doi.org/10.1097/JCP.0b013e31802e0002] [PMID: 17224716]
[11]
Dong H, Goico B, Martin M, Csernansky CA, Bertchume A, Csernansky JG. Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress. Neuroscience 127(3): 601-9. (2004).
[http://dx.doi.org/10.1016/j.neuroscience.2004.05.040] [PMID: 15283960]
[12]
Wang J, Zhang Y, Xu H, Zhu S, Wang H, He J, et al. Fluoxetine improves behavioral performance by suppressing the production of soluble β-amyloid in APP/PS1 mice. Curr Alzheimer Res 11(7): 672-80. (2014).
[http://dx.doi.org/10.2174/1567205011666140812114715] [PMID: 25115542]
[13]
Qiao J, Wang J, Wang H, Zhang Y, Zhu S, Adilijiang A, et al. Regulation of astrocyte pathology by fluoxetine prevents the deterioration of Alzheimer phenotypes in an APP/PS1 mouse model. Glia 64(2): 240-54. (2016).
[http://dx.doi.org/10.1002/glia.22926] [PMID: 26446044]
[14]
Jin L, Gao LF, Sun DS, Wu H, Wang Q, Ke D, et al. Long-term ameliorative effects of the antidepressant fluoxetine exposure on cognitive deficits in 3 × TgAD mice. Mol Neurobiol 54(6): 4160-71. (2017).
[http://dx.doi.org/10.1007/s12035-016-9952-9] [PMID: 27324897]
[15]
Sun DS, Gao LF, Jin L, Wu H, Wang Q, Zhou Y, et al. Fluoxetine administration during adolescence attenuates cognitive and synaptic deficits in adult 3×TgAD mice. Neuropharmacology 126: 200-12. (2017).
[http://dx.doi.org/10.1016/j.neuropharm.2017.08.037] [PMID: 28911966]
[16]
Huang M, Liang Y, Chen H, Xu B, Chai C, Xing P. The role of fluoxetine in activating Wnt/ β-Catenin signaling and repressing β-Amyloid production in an Alzheimer mouse model. Front Aging Neurosci 10: 164. (2018).
[http://dx.doi.org/10.3389/fnagi.2018.00164] [PMID: 29910725]
[17]
Ma J, Gao Y, Jiang L, Chao FL, Huang W, Zhou CN, et al. Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer’s disease mice. Oncotarget 8(17): 27676-92. (2017).
[http://dx.doi.org/10.18632/oncotarget.15398] [PMID: 28430602]
[18]
Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, Eersel JV, et al. Dendritic function of tau mediates amyloid-β toxicity in Alzheimer’s disease mouse models. Cell 142(3): 387-97. (2010).
[http://dx.doi.org/10.1016/j.cell.2010.06.036] [PMID: 20655099]
[19]
Ittner A, Ittner LM. Dendritic tau in Alzheimer’s disease. Neuron 99(1): 13-27. (2018).
[http://dx.doi.org/10.1016/j.neuron.2018.06.003] [PMID: 30001506]
[20]
Hoover BR, Reed MN, Su J, Penrod RD, Kotilinek LA, Grant MK, et al. Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron 68(6): 1067-81. (2010).
[http://dx.doi.org/10.1016/j.neuron.2010.11.030] [PMID: 21172610]
[21]
Hao J, Janssen WG, Tang Y, Roberts JA, McKay H, Lasley B, et al. Estrogen increases the number of spinophilin-immunoreactive spines in the hippocampus of young and aged female rhesus monkeys. J Comp Neurol 465(4): 540-50. (2003).
[http://dx.doi.org/10.1002/cne.10837] [PMID: 12975814]
[22]
Tang Y, Janssen WG, Hao J, Roberts JA, McKay H, Lasley B, et al. Estrogen replacement increases spinophilin-immunoreactive spine number in the prefrontal cortex of female rhesus monkeys. Cereb Cortex 14(2): 215-23. (2004).
[http://dx.doi.org/10.1093/cercor/bhg121] [PMID: 14704219]
[23]
West MJ, Slomianka L, Gundersen HJ. Unbiased stereological estimation of the total number of neurons in thesubdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231(4): 482-97. (1991).
[http://dx.doi.org/10.1002/ar.1092310411] [PMID: 1793176]
[24]
Paxinos G, Franklin KB. The mouse brain in stereotaxic coordinates. Gulf Professional Publishing. 2004..
[25]
Heggland I, Storkaas IS, Soligard HT, Kobro-Flatmoen A, Witter MP. Stereological estimation of neuron number and plaque load in the hippocampal region of a transgenic rat model of Alzheimer’s disease. Eur J Neurosci 41(9): 1245-62. (2015).
[http://dx.doi.org/10.1111/ejn.12876] [PMID: 25808554]
[26]
Gundersen HJ, Jensen EB, Kiêu K, Nielsen J. The efficiency of systematic sampling in stereology--reconsidered. J Microsc 193(Pt 3): 199-211. (1999).
[http://dx.doi.org/10.1046/j.1365-2818.1999.00457.x] [PMID: 10348656]
[27]
Ouimet CC, Katona I, Allen P, Freund TF, Greengard P. Cellular and subcellular distribution of spinophilin, a PP1 regulatory protein that bundles F-actin in dendritic spines. J Comp Neurol 479(4): 374-88. (2004).
[http://dx.doi.org/10.1002/cne.20313] [PMID: 15514983]
[28]
Vallejo D, Codocedo JF, Inestrosa NC. Posttranslational modifications regulate the postsynaptic localization of PSD-95. Mol Neurobiol 54(3): 1759-76. (2017).
[http://dx.doi.org/10.1007/s12035-016-9745-1] [PMID: 26884267]
[29]
Thiel G. Synapsin I, synapsin II, and synaptophysin: marker proteins of synaptic vesicles. Brain Pathol 3(1): 87-95. (1993).
[http://dx.doi.org/10.1111/j.1750-3639.1993.tb00729.x] [PMID: 7903586]
[30]
2018 Alzheimer’s disease facts and figures. Alzheimers Dement 12: 459-509. (2018).
[31]
Cummings J. Lessons learned from Alzheimer disease: clinical trials with negative outcomes. Clin Transl Sci 11(2): 147-52. (2018).
[http://dx.doi.org/10.1111/cts.12491] [PMID: 28767185]
[32]
Bourne J, Harris KM. Do thin spines learn to be mushroom spines that remember? Curr Opin Neurobiol 17(3): 381-6. (2007).
[http://dx.doi.org/10.1016/j.conb.2007.04.009] [PMID: 17498943]
[33]
Sala C, Segal M. Dendritic spines: the locus of structural and functional plasticity. Physiol Rev 94(1): 141-88. (2014).
[http://dx.doi.org/10.1152/physrev.00012.2013] [PMID: 24382885]
[34]
Hajszan T, Dow A, Warner-Schmidt JL, Szigeti-Buck K, Sallam NL, Parducz A, et al. Remodeling of hippocampal spine synapses in the rat learned helplessness model of depression. Biol Psychiatry 65(5): 392-400. (2009).
[http://dx.doi.org/10.1016/j.biopsych.2008.09.031] [PMID: 19006787]
[35]
Kempermann G, Kronenberg G. Depressed new neurons--adult hippocampal neurogenesis and a cellular plasticity hypothesis of major depression. Biol Psychiatry 54(5): 499-503. (2003).
[http://dx.doi.org/10.1016/S0006-3223(03)00319-6] [PMID: 12946878]
[36]
Berry KP, Nedivi E. Spine dynamics: are they all the same? Neuron 96(1): 43-55. (2017).
[http://dx.doi.org/10.1016/j.neuron.2017.08.008] [PMID: 28957675]
[37]
Bourne JN, Harris KM. Balancing structure and function at hippocampal dendritic spines. Annu Rev Neurosci 31: 47-67. (2008).
[http://dx.doi.org/10.1146/annurev.neuro.31.060407.125646] [PMID: 18284372]
[38]
Tackenberg C, Ghori A, Brandt R. Thin, stubby or mushroom: spine pathology in Alzheimer’s disease. Curr Alzheimer Res 6(3): 261-8. (2009).
[http://dx.doi.org/10.2174/156720509788486554] [PMID: 19519307]
[39]
Zhang H, Wu L, Pchitskaya E, Zakharova O, Saito T, Saido T, et al. Neuronal store-operated calcium entry and mushroom spine loss in Amyloid precursor protein knock-in mouse model of Alzheimer’s disease. J Neurosci 35(39): 13275-86. (2015).
[http://dx.doi.org/10.1523/JNEUROSCI.1034-15.2015] [PMID: 26424877]
[40]
Zhang H, Sun S, Wu L, Pchitskaya E, Zakharova O, Tacer KF, et al. Store-operated calcium channel complex in postsynaptic spines: a new therapeutic target for Alzheimer’s disease Treatment. J Neurosci 36(47): 11837-50. (2016).
[http://dx.doi.org/10.1523/JNEUROSCI.1188-16.2016] [PMID: 27881772]
[41]
Borczyk M. Śliwiń ska MA, Caly A, Bernas T, Radwanska K, 2019. Neuronal plasticity affects correlation between the size of dendritic spine and its postsynaptic density. Sci Rep 9(1): 1963. (2019).
[42]
Tapia-Rojas C, Cabezas-Opazo F, Deaton CA, Vergara EH, Johnson GVW, Quintanilla RA. It’s all about tau. Prog Neurobiol 175: 54-76. (2019).
[http://dx.doi.org/10.1016/j.pneurobio.2018.12.005] [PMID: 30605723]
[43]
Guo T, Noble W, Hanger DP. Roles of tau protein in health and disease. Acta Neuropathol 133(5): 665-704. (2017).
[http://dx.doi.org/10.1007/s00401-017-1707-9] [PMID: 28386764]
[44]
Wang Y, Mandelkow E. Tau in physiology and pathology. Nat Rev Neurosci 17(1): 5-21. (2016).
[http://dx.doi.org/10.1038/nrn.2015.1] [PMID: 26631930]
[45]
Lau DH, Hogseth M, Phillips EC, O’Neill MJ, Pooler AM, Noble W, et al. Critical residues involved in tau binding to fyn: implications for tau phosphorylation in Alzheimer’s disease. Acta Neuropathol Commun 4(1): 49. (2016).
[http://dx.doi.org/10.1186/s40478-016-0317-4] [PMID: 27193083]
[46]
Nygaard HB. Targeting Fyn kinase in Alzheimer’s disease. Biol Psychiatry 83(4): 369-76. (2018).
[http://dx.doi.org/10.1016/j.biopsych.2017.06.004] [PMID: 28709498]
[47]
Khan SS, Bloom GS. Tau: The center of a signaling nexus in Alzheimer’s disease. Front Neurosci 10: 31. (2016).
[http://dx.doi.org/10.3389/fnins.2016.00031] [PMID: 26903798]
[48]
Xia D, Li C, Götz J. Pseudophosphorylation of Tau at distinct epitopes or the presence of the P301L mutation targets the microtubule-associated protein Tau to dendritic spines. Biochim Biophys Acta 1852(5): 913-24. (2015).
[http://dx.doi.org/10.1016/j.bbadis.2014.12.017] [PMID: 25558816]
[49]
Hunter JM, Bowers WJ, Maarouf CL, Mastrangelo MA, Daugs ID, Kokjohn TA, et al. Biochemical and morphological characterization of the AβPP/PS/tau triple transgenic mouse model and its relevance to sporadic Alzheimer’s disease. J Alzheimers Dis 27(2): 361-76. (2011).
[http://dx.doi.org/10.3233/JAD-2011-110608] [PMID: 21860086]

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