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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

一种新型益生菌配方 BIOCG ，通过调节树突脊柱动力学来预防阿尔茨海默病相关的认知缺陷

卷 18, 期 7, 2021

发表于: 21 October, 2021

页: [558 - 572] 页: 15

弟呕挨: 10.2174/1567205018666211022091110

价格: $65

摘要

背景：脑-肠道-微生物组轴已成为肠道和/或微生物微环境中的扰动影响神经功能的重要途径。这种改变与多种神经精神疾病有关，包括抑郁症、焦虑症和阿尔茨海默病 (AD)，使用益生菌治疗这些疾病仍然很有希望。然而，肠道微环境对疾病发病机制和治疗的影响机制尚不清楚。 目的：本研究的目的是在 AD 小鼠模型中研究一种新型益生菌配方 BIOCG 对认知功能和病理生物学机制的影响，包括淀粉样蛋白加工和树突棘动力学。 方法：BIOCG给药3个月至3xTg或3xTg；通过行为测试和电生理学评估 Thy1-YFP AD 小鼠和功能结果。还评估了与 AD 发病机制相关的机制，包括树突棘形态和周转、淀粉样前体蛋白 (APP) 加工和小胶质细胞表型。最后，我们对益生菌处理后的粪便样本进行了测序，以评估对肠道微生物组成的影响，并将这些变化与上述措施相关联。 结果：用 BIOCG 治疗的小鼠表现出保留的认知能力和更强的长期增强 (LTP)、自发兴奋性突触后电流 (sEPSC) 和谷氨酸诱导的 LTP，表明功能和电生理效应。此外，我们观察到 AD 发病机制减弱，包括减少淀粉样蛋白 (Aβ) 负担，以及 BIOCG 治疗中更成熟的树突棘。我们对治疗组小胶质细胞数量和表型变化的发现表明，该制剂可能通过减弱神经炎症来调节其作用。测序数据证实，接受治疗的小鼠的肠道微生物组更加多样化，并且含有更大比例的“有益”细菌。 结论：总体而言，我们的结果表明 BIOCG 治疗可增强微生物多样性，并通过肠脑轴相互作用减轻神经炎症，从而改善 AD 发病机制的组织学和功能。

关键词: 阿尔茨海默病 (AD)、益生菌、体内成像、树突棘、突触可塑性、炎症。

« Previous Next »
[1]
World Alzheimer Report 2019. 2019. Available from: https://www.alzint.org/resource/world-alzheimer-report-2019/
[2]
Reddy PH, Oliver DMA. Amyloid beta and phosphorylated tau-induced defective autophagy and mitophagy in Alzheimer’s risease. Cells 2019; 8(5): E488.
[http://dx.doi.org/10.3390/cells8050488] [PMID: 31121890]
[3]
Mungenast AE, Siegert S, Tsai LH. Modeling Alzheimer’s disease with human induced pluripotent stem (iPS) cells. Mol Cell Neurosci 2016; 73: 13-31.
[http://dx.doi.org/10.1016/j.mcn.2015.11.010] [PMID: 26657644]
[4]
Dorsey ER, George BP, Leff B, Willis AW. The coming crisis: obtaining care for the growing burden of neurodegenerative conditions. Neurology 2013; 80(21): 1989-96.
[http://dx.doi.org/10.1212/WNL.0b013e318293e2ce] [PMID: 23616157]
[5]
Chen Y, Fu AKY, Ip NY. Synaptic dysfunction in Alzheimer’s disease: Mechanisms and therapeutic strategies. Pharmacol Ther 2019; 195: 186-98.
[http://dx.doi.org/10.1016/j.pharmthera.2018.11.006] [PMID: 30439458]
[6]
Kokubo H, Kayed R, Glabe CG, Yamaguchi H. Soluble Abeta oligomers ultrastructurally localize to cell processes and might be related to synaptic dysfunction in Alzheimer’s disease brain. Brain Res 2005; 1031(2): 222-8.
[http://dx.doi.org/10.1016/j.brainres.2004.10.041] [PMID: 15649447]
[7]
Bomba M, Ciavardelli D, Silvestri E, et al. Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals. Cell Death Dis 2013; 4: e612.
[http://dx.doi.org/10.1038/cddis.2013.139] [PMID: 23640454]
[8]
Lecca D, Bader M, Tweedie D, et al. (-)-Phenserine and the prevention of pre-programmed cell death and neuroinflammation in mild traumatic brain injury and Alzheimer’s disease challenged mice. Neurobiol Dis 2019; 130: 104528.
[http://dx.doi.org/10.1016/j.nbd.2019.104528] [PMID: 31295555]
[9]
Mueller SG, Schuff N, Yaffe K, Madison C, Miller B, Weiner MW. Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer’s disease. Hum Brain Mapp 2010; 31(9): 1339-47.
[http://dx.doi.org/10.1002/hbm.20934] [PMID: 20839293]
[10]
Cho C, MacDonald R, Shang J, Cho MJ, Chalifour LE, Paudel HK. Early growth response-1-mediated down-regulation of drebrin correlates with loss of dendritic spines. J Neurochem 2017; 142(1): 56-73.
[http://dx.doi.org/10.1111/jnc.14031] [PMID: 28369888]
[11]
Hooper PL, Durham HD, Török Z, Hooper PL, Crul T, Vígh L. The central role of heat shock factor 1 in synaptic fidelity and memory consolidation. Cell Stress Chaperones 2016; 21(5): 745-53.
[http://dx.doi.org/10.1007/s12192-016-0709-1] [PMID: 27283588]
[12]
Huo R, Zeng B, Zeng L, et al. Microbiota modulate anxiety-like behavior and endocrine abnormalities in hypothalamic-pituitary-adrenal axis. Front Cell Infect Microbiol 2017; 7: 489.
[http://dx.doi.org/10.3389/fcimb.2017.00489] [PMID: 29250490]
[13]
Diaz Heijtz R, Wang S, Anuar F, et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci USA 2011; 108(7): 3047-52.
[http://dx.doi.org/10.1073/pnas.1010529108] [PMID: 21282636]
[14]
Bercik P. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 2011; 141(2): 599-609.
[http://dx.doi.org/10.1053/j.gastro.2011.04.052]
[15]
Vogt NM, Kerby RL, Dill-McFarland KA, et al. Gut microbiome alterations in Alzheimer’s disease. Sci Rep 2017; 7(1): 13537.
[http://dx.doi.org/10.1038/s41598-017-13601-y] [PMID: 29051531]
[16]
Akbari E, Asemi Z, Daneshvar Kakhaki R, et al. Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer’s disease: A randomized, double-blind and controlled trial. Front Aging Neurosci 2016; 8: 256.
[http://dx.doi.org/10.3389/fnagi.2016.00256] [PMID: 27891089]
[17]
Minter MR, Hinterleitner R, Meisel M, et al. Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APPSWE/PS1ΔE9 murine model of Alzheimer’s disease. Sci Rep 2017; 7(1): 10411.
[http://dx.doi.org/10.1038/s41598-017-11047-w] [PMID: 28874832]
[18]
Mo M, Eyo UB, Xie M, et al. Microglial P2Y12 receptor regulates seizure-induced neurogenesis and immature neuronal projections. J Neurosci 2019; 39(47): 9453-64.
[http://dx.doi.org/10.1523/JNEUROSCI.0487-19.2019] [PMID: 31597724]
[19]
Eyo UB, Peng J, Swiatkowski P, Mukherjee A, Bispo A, Wu LJ. Neuronal hyperactivity recruits microglial processes via neuronal NMDA receptors and microglial P2Y12 receptors after status epilepticus. J Neurosci 2014; 34(32): 10528-40.
[http://dx.doi.org/10.1523/JNEUROSCI.0416-14.2014] [PMID: 25100587]
[20]
Yoshihara Y, De Roo M, Muller D. Dendritic spine formation and stabilization. Curr Opin Neurobiol 2009; 19(2): 146-53.
[http://dx.doi.org/10.1016/j.conb.2009.05.013] [PMID: 19523814]
[21]
Pchitskaya E, Bezprozvanny I. Dendritic spines shape analysis-classification or clusterization? Perspective. Front Synaptic Neurosci 2020; 12: 31.
[http://dx.doi.org/10.3389/fnsyn.2020.00031] [PMID: 33117142]
[22]
Kwon HB, Sabatini BL. Glutamate induces de novo growth of functional spines in developing cortex. Nature 2011; 474(7349): 100-4.
[http://dx.doi.org/10.1038/nature09986] [PMID: 21552280]
[23]
Wu Q, Sun M, Bernard LP, Zhang H. Postsynaptic density 95 (PSD-95) serine 561 phosphorylation regulates a conformational switch and bidirectional dendritic spine structural plasticity. J Biol Chem 2017; 292(39): 16150-60.
[http://dx.doi.org/10.1074/jbc.M117.782490] [PMID: 28790172]
[24]
DiBona VL, Zhu W, Shah MK, et al. Loss of Par1b/MARK2 primes microglia during brain development and enhances their sensitivity to injury. J Neuroinflammation 2019; 16(1): 11.
[http://dx.doi.org/10.1186/s12974-018-1390-3] [PMID: 30654821]
[25]
Kauppinen TM, Swanson RA. Poly(ADP-ribose) polymerase-1 promotes microglial activation, proliferation, and matrix metalloproteinase-9-mediated neuron death. J Immunol 2005; 174(4): 2288-96.
[http://dx.doi.org/10.4049/jimmunol.174.4.2288] [PMID: 15699164]
[26]
Kauppinen TM, Suh SW, Higashi Y, et al. Poly(ADP-ribose)polymerase-1 modulates microglial responses to amyloid β. J Neuroinflammation 2011; 8(1): 152.
[http://dx.doi.org/10.1186/1742-2094-8-152] [PMID: 22051244]
[27]
Wang XF, Liu JJ, Xia J, Liu J, Mirabella V, Pang ZP. Endogenous glucagon-like peptide-1 suppresses high-fat food intake by reducing synaptic drive onto mesolimbic dopamine neurons. Cell Rep 2015; 12(5): 726-33.
[http://dx.doi.org/10.1016/j.celrep.2015.06.062] [PMID: 26212334]
[28]
Maqueshudul Haque Bhuiyan M, Mohibbullah M, Hannan MA, et al. Undaria pinnatifida promotes spinogenesis and synaptogenesis and potentiates functional presynaptic plasticity in hippocampal neurons. Am J Chin Med 2015; 43(3): 529-42.
[http://dx.doi.org/10.1142/S0192415X15500330] [PMID: 25967666]
[29]
Jamet S, Bubnell J, Pfister P, Tomoiaga D, Rogers ME, Feinstein P. In vitro mutational analysis of the β2 adrenergic receptor, an in vivo surrogate odorant receptor. PLoS One 2015; 10(10): e0141696.
[http://dx.doi.org/10.1371/journal.pone.0141696] [PMID: 26513247]
[30]
Chunchai T, Thunapong W, Yasom S, et al. Decreased microglial activation through gut-brain axis by prebiotics, probiotics, or synbiotics effectively restored cognitive function in obese-insulin resistant rats. J Neuroinflammation 2018; 15(1): 11.
[http://dx.doi.org/10.1186/s12974-018-1055-2] [PMID: 29316965]
[31]
Sun M, Asghar SZ, Zhang H. The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb. Neurobiol Dis 2016; 93: 1-11.
[http://dx.doi.org/10.1016/j.nbd.2016.03.022] [PMID: 27072891]
[32]
Kaur H, Nagamoto-Combs K, Golovko S, Golovko MY, Klug MG, Combs CK. Probiotics ameliorate intestinal pathophysiology in a mouse model of Alzheimer’s disease. Neurobiol Aging 2020; 92: 114-34.
[http://dx.doi.org/10.1016/j.neurobiolaging.2020.04.009] [PMID: 32417748]
[33]
Xiao J, Katsumata N, Bernier F, et al. Probiotic bifidobacterium breve in improving cognitive functions of older adults with suspected mild cognitive impairment: A randomized, double-blind, placebo-controlled trial. J Alzheimer's Dis 2020; 77(1): 137-47.
[http://dx.doi.org/10.3233/JAD-200488] [PMID: 32623402]
[34]
Kobayashi Y, Sugahara H, Shimada K, et al. Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer’s disease. Sci Rep 2017; 7(1): 13510.
[http://dx.doi.org/10.1038/s41598-017-13368-2] [PMID: 29044140]
[35]
Guilherme MDS, Nguyen VTT, Reinhardt C, Endres K. Impact of gut microbiome manipulation in 5xFAD mice on alzheimer’s disease-like pathology. Microorganisms 2021; 9(4): 815.
[http://dx.doi.org/10.3390/microorganisms9040815] [PMID: 33924322]
[36]
Andreyeva A, Nieweg K, Horstmann K, et al. C-terminal fragment of N-cadherin accelerates synapse destabilization by amyloid-β. Brain 2012; 135(Pt 7): 2140-54.
[http://dx.doi.org/10.1093/brain/aws120] [PMID: 22637581]
[37]
Ramalho RM, Nunes AF, Dias RB, et al. Tauroursodeoxycholic acid suppresses amyloid β-induced synaptic toxicity in vitro and in APP/PS1 mice. Neurobiol Aging 2013; 34(2): 551-61.
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.04.018] [PMID: 22621777]
[38]
Nomura I, Takechi H, Kato N. Intraneuronally injected amyloid β inhibits long-term potentiation in rat hippocampal slices. J Neurophysiol 2012; 107(9): 2526-31.
[http://dx.doi.org/10.1152/jn.00589.2011] [PMID: 22338026]
[39]
Firbank MJ, Blamire AM, Teodorczuk A, Teper E, Mitra D, O’Brien JT. Diffusion tensor imaging in Alzheimer’s disease and dementia with Lewy bodies. Psychiatry Res 2011; 194(2): 176-83.
[http://dx.doi.org/10.1016/j.pscychresns.2011.08.002] [PMID: 21955457]
[40]
Mattia D, Babiloni F, Romigi A, et al. Quantitative EEG and dynamic susceptibility contrast MRI in Alzheimer’s disease: a correlative study. Clin Neurophysiol 2003; 114(7): 1210-6.
[http://dx.doi.org/10.1016/S1388-2457(03)00085-3] [PMID: 12842717]
[41]
Rezaei Asl Z, Sepehri G, Salami M. Probiotic treatment improves the impaired spatial cognitive performance and restores synaptic plasticity in an animal model of Alzheimer’s disease. Behav Brain Res 2019; 376: 112183.
[http://dx.doi.org/10.1016/j.bbr.2019.112183] [PMID: 31472194]
[42]
Sun N, Ni X, Wang H, et al. Probiotic Lactobacillus johnsonii BS15 prevents memory dysfunction induced by chronic high-fluorine intake through modulating intestinal environment and improving gut development. Probiotics Antimicrob Proteins 2020; 12(4): 1420-38.
[http://dx.doi.org/10.1007/s12602-020-09644-9] [PMID: 32166711]
[43]
Varnum MM, Ikezu T. The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer’s disease brain. Arch Immunol Ther Exp (Warsz) 2012; 60(4): 251-66.
[http://dx.doi.org/10.1007/s00005-012-0181-2] [PMID: 22710659]
[44]
Streit WJ, Xue QS. Human CNS immune senescence and neurodegeneration. Curr Opin Immunol 2014; 29: 93-6.
[http://dx.doi.org/10.1016/j.coi.2014.05.005] [PMID: 24908174]
[45]
Jin SC, Benitez BA, Karch CM, et al. Coding variants in TREM2 increase risk for Alzheimer’s disease. Hum Mol Genet 2014; 23(21): 5838-46.
[http://dx.doi.org/10.1093/hmg/ddu277] [PMID: 24899047]
[46]
Condic M, Oberstein TJ, Herrmann M, et al. N-truncation and pyroglutaminylation enhances the opsonizing capacity of Aβ-peptides and facilitates phagocytosis by macrophages and microglia. Brain Behav Immun 2014; 41: 116-25.
[http://dx.doi.org/10.1016/j.bbi.2014.05.003] [PMID: 24876064]
[47]
Isidro RA, Lopez A, Cruz ML, et al. The probiotic VSL#3 modulates colonic macrophages, inflammation, and microflora in acute trinitrobenzene sulfonic acid colitis. J Histochem Cytochem 2017; 65(8): 445-61.
[http://dx.doi.org/10.1369/0022155417718542] [PMID: 28692320]
[48]
Liu YW, Liu WH, Wu CC, et al. Psychotropic effects of Lactobacillus plantarum PS128 in early life-stressed and naïve adult mice. Brain Res 2016; 1631: 1-12.
[http://dx.doi.org/10.1016/j.brainres.2015.11.018] [PMID: 26620542]
[49]
Guo C, Yang ZH, Zhang S, et al. Intranasal lactoferrin enhances α-secretase-dependent amyloid precursor protein processing via the ERK1/2-CREB and HIF-1α pathways in an Alzheimer’s disease mouse model. Neuropsychopharmacology 2017; 42(13): 2504-15.
[http://dx.doi.org/10.1038/npp.2017.8] [PMID: 28079060]
[50]
Ries M, Loiola R, Shah UN, Gentleman SM, Solito E, Sastre M. The anti-inflammatory Annexin A1 induces the clearance and degradation of the amyloid-β peptide. J Neuroinflammation 2016; 13(1): 234.
[http://dx.doi.org/10.1186/s12974-016-0692-6] [PMID: 27590054]
[51]
Peng Y, Sun J, Hon S, et al. L-3-n-butylphthalide improves cognitive impairment and reduces amyloid-beta in a transgenic model of Alzheimer’s disease. J Neurosci 2010; 30(24): 8180-9.
[http://dx.doi.org/10.1523/JNEUROSCI.0340-10.2010] [PMID: 20554868]
[52]
Sun M, Huang C, Wang H, Zhang H. Par3 regulates polarized convergence between APP and BACE1 in hippocampal neurons. Neurobiol Aging 2019; 77: 87-93.
[http://dx.doi.org/10.1016/j.neurobiolaging.2019.01.023] [PMID: 30784815]
[53]
Sun M, Zhang H. Par3 and aPKC regulate BACE1 endosome-to-TGN trafficking through PACS1. Neurobiol Aging 2017; 60: 129-40.
[http://dx.doi.org/10.1016/j.neurobiolaging.2017.08.024] [PMID: 28946017]
[54]
Wei MY, Shi S, Liang C, et al. The microbiota and microbiome in pancreatic cancer: more influential than expected. Mol Cancer 2019; 18(1): 97.
[http://dx.doi.org/10.1186/s12943-019-1008-0] [PMID: 31109338]
[55]
Huang SY, Chen LH, Wang MF, et al. Lactobacillus paracasei PS23 delays progression of age-related cognitive decline in senescence accelerated mouse prone 8 (SAMP8) mice. Nutrients 2018; 10(7): E894.
[http://dx.doi.org/10.3390/nu10070894] [PMID: 30002347]
[56]
Andisi VF, Hinojosa CA, de Jong A, Kuipers OP, Orihuela CJ, Bijlsma JJ. Pneumococcal gene complex involved in resistance to extracellular oxidative stress. Infect Immun 2012; 80(3): 1037-49.
[http://dx.doi.org/10.1128/IAI.05563-11] [PMID: 22215735]
[57]
Salehipour Z, Haghmorad D, Sankian M, et al. Bifidobacterium animalis in combination with human origin of Lactobacillus plantarum ameliorate neuroinflammation in experimental model of multiple sclerosis by altering CD4+ T cell subset balance. Biomed Pharmacother 2017; 95: 1535-48.
[http://dx.doi.org/10.1016/j.biopha.2017.08.117] [PMID: 28946394]
[58]
O’Hagan C, Li JV, Marchesi JR, Plummer S, Garaiova I, Good MA. Long-term multi-species Lactobacillus and Bifidobacterium dietary supplement enhances memory and changes regional brain metabolites in middle-aged rats. Neurobiol Learn Mem 2017; 144: 36-47.
[http://dx.doi.org/10.1016/j.nlm.2017.05.015] [PMID: 28602659]
[59]
Cheng R, Xu T, Zhang Y, et al. Lactobacillus rhamnosus GG and Bifidobacterium bifidum TMC3115 can affect development of hippocampal neurons cultured in vitro in a strain-dependent manner. Probiotics Antimicrob Proteins 2020; 12(2): 589-99.
[http://dx.doi.org/10.1007/s12602-019-09571-4] [PMID: 31286435]
[60]
Mohammadi G, Dargahi L, Naserpour T, et al. Probiotic mixture of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 attenuates hippocampal apoptosis induced by lipopolysaccharide in rats. Int Microbiol 2019; 22(3): 317-23.
[http://dx.doi.org/10.1007/s12602-019-09571-4] [PMID: 30810993]
[61]
Tamtaji OR, Heidari-Soureshjani R, Mirhosseini N, et al. Probiotic and selenium co-supplementation, and the effects on clinical, metabolic and genetic status in Alzheimer’s disease: a randomized, double-blind, controlled trial. Clin Nutr 2019; 38(6): 2569-75.
[http://dx.doi.org/10.1016/j.clnu.2018.11.034] [PMID: 30642737]
[62]
Athari Nik Azm S, Djazayeri A, Safa M, et al. Probiotics improve insulin resistance status in an experimental model of Alzheimer’s disease. Med J Islam Repub Iran 2017; 31: 103.
[http://dx.doi.org/10.14196/mjiri.31.103] [PMID: 29951404]
[63]
van Beek AA, Sovran B, Hugenholtz F, et al. Supplementation with Lactobacillus plantarum WCFS1 prevents decline of mucus barrier in colon of accelerated aging Ercc1-/Δ7 Mice. Front Immunol 2016; 7: 408.
[http://dx.doi.org/10.3389/fimmu.2016.00408] [PMID: 27774093]

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