Login Register Cart 0
Generic placeholder image

当代阿耳茨海默病研究

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in English
Research Article

高脂肪饮食会加重 APP/PS1 小鼠的 AD 相关致病过程

卷 18, 期 4, 2021

发表于: 23 September, 2021

页: [310 - 325] 页: 16

弟呕挨: 10.2174/1567205018666210628100812

价格: $65

摘要

背景：阿尔茨海默病 (AD) 是最常见的神经退行性疾病，消极的生活方式因素可能导致其发病。来自人类和小鼠模型的大量证据表明，与高脂肪饮食 (HFD) 相关的胰岛素抵抗 (IR) 会增加患 AD 和与年龄相关的淀粉样蛋白生成的风险。

目的：本研究的目的是证实和阐明 HFD 对 AD 模型小鼠淀粉样变性和认知缺陷的影响。

方法：我们在此表明，四个月的 HFD 喂养会增加 APP/PS1 小鼠（用作 AD 模型）的外周和大脑的 IR。同时，长期HFD会加剧APP/PS1小鼠的认知缺陷并损害树突完整性和突触蛋白的表达。此外，HFD 诱导 β-分泌酶 (BACE1) 表达增加和胰岛素降解酶 (IDE) 表达减少，导致 β-淀粉样蛋白 (Aβ) 积累。

结论：我们的数据表明，长期 HFD 伴随 IR 会促进 Aβ 毒性和认知缺陷，表明可改变的生活方式危害，如 HFD 诱导的 IR 可能有助于 AD 发病机制。

关键词: 阿尔茨海默病 (AD)、认知障碍、高脂肪饮食 (HFD)、胰岛素抵抗 (IR)、β-淀粉样蛋白 (Aβ)、胰岛素降解酶 (IDE)、β-分泌酶 (BACE1)。

« Previous Next »
[1]
Long JM, Holtzman DM. Alzheimer disease: An update on pathobiology and treatment strategies. Cell 2019; 179(2): 312-39.
[http://dx.doi.org/10.1016/j.cell.2019.09.001] [PMID: 31564456]
[2]
Jack CR Jr, Wiste HJ, Schwarz CG, et al. Longitudinal tau PET in ageing and Alzheimer’s disease. Brain 2018; 141(5): 1517-28.
[http://dx.doi.org/10.1093/brain/awy059] [PMID: 29538647]
[3]
Duyckaerts C, Delatour B, Potier MC. Classification and basic pathology of Alzheimer disease. Acta Neuropathol 2009; 118(1): 5-36.
[http://dx.doi.org/10.1007/s00401-009-0532-1] [PMID: 19381658]
[4]
Liu L, Ding L, Rovere M, Wolfe MS, Selkoe DJ. A cellular complex of BACE1 and γ-secretase sequentially generates Aβ from its full-length precursor. J Cell Biol 2019; 218(2): 644-63.
[http://dx.doi.org/10.1083/jcb.201806205] [PMID: 30626721]
[5]
Selkoe DJ. Biochemistry and molecular biology of amyloid beta-protein and the mechanism of Alzheimer’s disease. Handb Clin Neurol 2008; 89: 245-60.
[http://dx.doi.org/10.1016/S0072-9752(07)01223-7] [PMID: 18631749]
[6]
Alonso AC, Grundke-Iqbal I, Iqbal K. Alzheimer’s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat Med 1996; 2(7): 783-7.
[http://dx.doi.org/10.1038/nm0796-783] [PMID: 8673924]
[7]
Hoover BR, Reed MN, Su J, et al. Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron 2010; 68(6): 1067-81.
[http://dx.doi.org/10.1016/j.neuron.2010.11.030] [PMID: 21172610]
[8]
Cordner ZA, Tamashiro KL. Effects of high-fat diet exposure on learning & memory. Physiol Behav 2015; 152(Pt B): 363-71.
[http://dx.doi.org/10.1016/j.physbeh.2015.06.008]
[9]
Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol 2011; 10(9): 819-28.
[http://dx.doi.org/10.1016/S1474-4422(11)70072-2] [PMID: 21775213]
[10]
Morris MC, Evans DA, Bienias JL, et al. Dietary fats and the risk of incident Alzheimer disease. Arch Neurol 2003; 60(2): 194-200.
[http://dx.doi.org/10.1001/archneur.60.2.194] [PMID: 12580703]
[11]
Ettcheto M, Petrov D, Pedrós I, et al. Evaluation of neuropathological effects of a high-fat diet in a presymptomatic alzheimer’s disease stage in APP/PS1 mice. J Alzheimers Dis 2016; 54(1): 233-51.
[http://dx.doi.org/10.3233/JAD-160150] [PMID: 27567882]
[12]
Allen KV, Frier BM, Strachan MW. The relationship between type 2 diabetes and cognitive dysfunction: Longitudinal studies and their methodological limitations. Eur J Pharmacol 2004; 490(1-3): 169-75.
[http://dx.doi.org/10.1016/j.ejphar.2004.02.054] [PMID: 15094083]
[13]
Holland WL, Brozinick JT, Wang LP, et al. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab 2007; 5(3): 167-79.
[http://dx.doi.org/10.1016/j.cmet.2007.01.002] [PMID: 17339025]
[14]
Arnold SE, Arvanitakis Z, Macauley-Rambach SL, et al. Brain insulin resistance in type 2 diabetes and Alzheimer disease: Concepts and conundrums. Nat Rev Neurol 2018; 14(3): 168-81.
[http://dx.doi.org/10.1038/nrneurol.2017.185] [PMID: 29377010]
[15]
Biessels GJ, Reagan LP. Hippocampal insulin resistance and cognitive dysfunction. Nat Rev Neurosci 2015; 16(11): 660-71.
[http://dx.doi.org/10.1038/nrn4019] [PMID: 26462756]
[16]
Fu Z, Wu J, Nesil T, Li MD, Aylor KW, Liu Z. Long-term high-fat diet induces hippocampal microvascular insulin resistance and cognitive dysfunction. Am J Physiol Endocrinol Metab 2017; 312(2): E89-97.
[http://dx.doi.org/10.1152/ajpendo.00297.2016] [PMID: 27899343]
[17]
Kullmann S, Heni M, Hallschmid M, Fritsche A, Preissl H, Häring HU. Brain insulin resistance at the crossroads of metabolic and cognitive disorders in humans. Physiol Rev 2016; 96(4): 1169-209.
[http://dx.doi.org/10.1152/physrev.00032.2015] [PMID: 27489306]
[18]
Qiu WQ, Folstein MF. Insulin, insulin-degrading enzyme and amyloid-beta peptide in Alzheimer’s disease: Review and hypothesis. Neurobiol Aging 2006; 27(2): 190-8.
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.01.004] [PMID: 16399206]
[19]
Hulse RE, Ralat LA, Wei-Jen T. Structure, function, and regulation of insulin-degrading enzyme. Vitam Horm 2009; 80: 635-48.
[http://dx.doi.org/10.1016/S0083-6729(08)00622-5] [PMID: 19251053]
[20]
Farris W, Mansourian S, Chang Y, et al. Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci USA 2003; 100(7): 4162-7.
[http://dx.doi.org/10.1073/pnas.0230450100] [PMID: 12634421]
[21]
Kim B, Figueroa-Romero C, Pacut C, Backus C, Feldman EL. Insulin Resistance prevents AMPK-induced tau dephosphorylation through Akt-mediated increase in AMPKSer-485 phosphorylation. J Biol Chem 2015; 290(31): 19146-57.
[http://dx.doi.org/10.1074/jbc.M115.636852] [PMID: 26100639]
[22]
Kim B, Sims-Robinson C, Backus C, Oh SS, Feldman EL. Insulin resistance (InsR) increases the phosphorylation of APP and Tau: Possible connection of InsR and cognitive deficit. Diabetes 2014; 63: A507-07.
[23]
Deng Y, Li B, Liu Y, Iqbal K, Grundke-Iqbal I, Gong CX. Dysregulation of insulin signaling, glucose transporters, O-GlcNAcylation, and phosphorylation of tau and neurofilaments in the brain: Implication for Alzheimer’s disease. Am J Pathol 2009; 175(5): 2089-98.
[http://dx.doi.org/10.2353/ajpath.2009.090157] [PMID: 19815707]
[24]
Schubert M, Gautam D, Surjo D, et al. Role for neuronal insulin resistance in neurodegenerative diseases. Proc Natl Acad Sci USA 2004; 101(9): 3100-5.
[http://dx.doi.org/10.1073/pnas.0308724101] [PMID: 14981233]
[25]
Schubert M, Brazil DP, Burks DJ, et al. Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation. J Neurosci 2003; 23(18): 7084-92.
[http://dx.doi.org/10.1523/JNEUROSCI.23-18-07084.2003] [PMID: 12904469]
[26]
Spielman LJ, Little JP, Klegeris A. Inflammation and insulin/IGF-1 resistance as the possible link between obesity and neurodegeneration. J Neuroimmunol 2014; 273(1-2): 8-21.
[http://dx.doi.org/10.1016/j.jneuroim.2014.06.004] [PMID: 24969117]
[27]
Bao J, Liu W, Zhou HY, et al. Epigallocatechin-3-gallate alleviates cognitive deficits in APP/PS1 mice. Curr Med Sci 2020; 40(1): 18-27.
[http://dx.doi.org/10.1007/s11596-020-2142-z] [PMID: 32166661]
[28]
Hughey CC, Hittel DS, Johnsen VL, Shearer J. Hyperinsulinemic-euglycemic clamp in the conscious rat. J Vis Exp 2011; 7(48): 2432.
[PMID: 21339723]
[29]
Segal M. Dendritic spines: Morphological building blocks of memory. Neurobiol Learn Mem 2017; 138: 3-9.
[http://dx.doi.org/10.1016/j.nlm.2016.06.007] [PMID: 27311757]
[30]
Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H. Structural basis of long-term potentiation in single dendritic spines. Nature 2004; 429(6993): 761-6.
[http://dx.doi.org/10.1038/nature02617] [PMID: 15190253]
[31]
Lisman J, Buzsaki G, Eichenbaum H, Nadel L, Ranganath C, Redish AD. Viewpoints: How the hippocampus contributes to memory, navigation and cognition (vol 20, pg 1434, 2017). Nat Neurosci 2018; 21(7): 1018-8.
[http://dx.doi.org/10.1038/s41593-017-0034-8] [PMID: 29263406]
[32]
Jankowsky JL, Fadale DJ, Anderson J, et al. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: Evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 2004; 13(2): 159-70.
[http://dx.doi.org/10.1093/hmg/ddh019] [PMID: 14645205]
[33]
Holtzman DM, Bales KR, Paul SM, DeMattos RB. Abeta immunization and anti-Abeta antibodies: Potential therapies for the prevention and treatment of Alzheimer’s disease. Adv Drug Deliv Rev 2002; 54(12): 1603-13.
[http://dx.doi.org/10.1016/S0169-409X(02)00158-8] [PMID: 12453677]
[34]
Kurochkin IV, Guarnera E, Berezovsky IN. Insulin-degrading enzyme in the fight against alzheimer’s disease. Trends Pharmacol Sci 2018; 39(1): 49-58.
[http://dx.doi.org/10.1016/j.tips.2017.10.008] [PMID: 29132916]
[35]
Kurt MA, Davies DC, Kidd M, Duff K, Howlett DR. Hyperphosphorylated tau and paired helical filament-like structures in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes. Neurobiol Dis 2003; 14(1): 89-97.
[http://dx.doi.org/10.1016/S0969-9961(03)00084-6] [PMID: 13678670]
[36]
Hassing LB, Dahl AK, Thorvaldsson V, et al. Overweight in midlife and risk of dementia: A 40-year follow-up study. Int J Obes 2009; 33(8): 893-8.
[http://dx.doi.org/10.1038/ijo.2009.104] [PMID: 19506566]
[37]
Kingwell K. Overweight or obesity during midlife is associated with late-life dementia. Nat Rev Neurol 2011; 7(6): 299.
[http://dx.doi.org/10.1038/nrneurol.2011.74] [PMID: 21654708]
[38]
Ramos-Rodriguez JJ, Ortiz O, Jimenez-Palomares M, et al. Differential central pathology and cognitive impairment in pre-diabetic and diabetic mice. Psychoneuroendocrinology 2013; 38(11): 2462-75.
[http://dx.doi.org/10.1016/j.psyneuen.2013.05.010] [PMID: 23790682]
[39]
Barron AM, Rosario ER, Elteriefi R, Pike CJ. Sex-specific effects of high fat diet on indices of metabolic syndrome in 3xTg-AD mice: Implications for Alzheimer’s disease. PLoS One 2013; 8(10): e78554.
[http://dx.doi.org/10.1371/journal.pone.0078554] [PMID: 24205258]
[40]
Artunc F, Schleicher E, Weigert C, Fritsche A, Stefan N, Häring HU. The impact of insulin resistance on the kidney and vasculature. Nat Rev Nephrol 2016; 12(12): 721-37.
[http://dx.doi.org/10.1038/nrneph.2016.145] [PMID: 27748389]
[41]
Han X, Ma Y, Liu X, et al. Changes in insulin-signaling transduction pathway underlie learning/memory deficits in an Alzheimer’s disease rat model. J Neural Transm (Vienna) 2012; 119(11): 1407-16.
[http://dx.doi.org/10.1007/s00702-012-0803-1] [PMID: 22527777]
[42]
Pilcher H. Alzheimer’s disease could be “type 3 diabetes”. Lancet Neurol 2006; 5(5): 388-9.
[http://dx.doi.org/10.1016/S1474-4422(06)70434-3] [PMID: 16639835]
[43]
Craft S. Insulin resistance and Alzheimer’s disease pathogenesis: Potential mechanisms and implications for treatment. Curr Alzheimer Res 2007; 4(2): 147-52.
[http://dx.doi.org/10.2174/156720507780362137] [PMID: 17430239]
[44]
Bosco D, Fava A, Plastino M, Montalcini T, Pujia A. Possible implications of insulin resistance and glucose metabolism in Alzheimer’s disease pathogenesis. J Cell Mol Med 2011; 15(9): 1807-21.
[http://dx.doi.org/10.1111/j.1582-4934.2011.01318.x] [PMID: 21435176]
[45]
Duman CH, Duman RS. Spine synapse remodeling in the pathophysiology and treatment of depression. Neurosci Lett 2015; 601: 20-9.
[http://dx.doi.org/10.1016/j.neulet.2015.01.022] [PMID: 25582786]
[46]
Qiao H, Li MX, Xu C, Chen HB, An SC, Ma XM. Dendritic spines in depression: What we learned from animal models. Neural Plast 2016; 2016: 8056370.
[http://dx.doi.org/10.1155/2016/8056370] [PMID: 26881133]
[47]
Song C, Ehlers VL, Moyer JR Jr. Trace fear conditioning differentially modulates intrinsic excitability of medial prefrontal cortex-basolateral complex of amygdala projection neurons in infralimbic and prelimbic cortices. J Neurosci 2015; 35(39): 13511-24.
[http://dx.doi.org/10.1523/JNEUROSCI.2329-15.2015] [PMID: 26424895]
[48]
Henley JM, Seager R, Nakamura Y, Talandyte K, Nair J, Wilkinson KA. Sumoylation of synaptic and synapse-associated proteins: An update. J Neurochem 2021; 156(2): 145-61.
[http://dx.doi.org/10.1111/jnc.15103] [PMID: 32538470]
[49]
Vekrellis K, Ye Z, Qiu WQ, et al. Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme. J Neurosci 2000; 20(5): 1657-65.
[http://dx.doi.org/10.1523/JNEUROSCI.20-05-01657.2000] [PMID: 10684867]
[50]
Gasparini L, Gouras GK, Wang R, et al. Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci 2001; 21(8): 2561-70.
[http://dx.doi.org/10.1523/JNEUROSCI.21-08-02561.2001] [PMID: 11306609]
[51]
Peila R, Rodriguez BL, White LR, Launer LJ. Fasting insulin and incident dementia in an elderly population of Japanese-American men. Neurology 2004; 63(2): 228-33.
[http://dx.doi.org/10.1212/01.WNL.0000129989.28404.9B] [PMID: 15277613]
[52]
Chua LM, Lim ML, Chong PR, Hu ZP, Cheung NS, Wong BS. Impaired neuronal insulin signaling precedes Aβ42 accumulation in female AβPPsw/PS1ΔE9 mice. J Alzheimers Dis 2012; 29(4): 783-91.
[http://dx.doi.org/10.3233/JAD-2012-111880] [PMID: 22337827]
[53]
Stanley M, Macauley SL, Holtzman DM. Changes in insulin and insulin signaling in Alzheimer’s disease: Cause or consequence? J Exp Med 2016; 213(8): 1375-85.
[http://dx.doi.org/10.1084/jem.20160493] [PMID: 27432942]
[54]
Hoffmeister A, Tuennemann J, Sommerer I, et al. Genetic and biochemical evidence for a functional role of BACE1 in the regulation of insulin mRNA expression. Obesity (Silver Spring) 2013; 21(12): E626-33.
[http://dx.doi.org/10.1002/oby.20482] [PMID: 23596049]
[55]
Abe H, Ishida Y, Nonaka H, Iwasaki T. Functional difference between rat perirhinal cortex and hippocampus in object and place discrimination tasks. Behav Brain Res 2009; 197(2): 388-97.
[http://dx.doi.org/10.1016/j.bbr.2008.10.012] [PMID: 18984009]
[56]
Polyanskii VB, Evtikhin DV, Sokolov EN, Kryuchkova AV. Limited plasticity of difference neurons in the visual cortex and hippocampus in rabbits during the oddball (random substitutions) test. Neurosci Behav Physiol 2006; 36(5): 441-8.
[http://dx.doi.org/10.1007/s11055-006-0037-5] [PMID: 16645755]
[57]
Zhang Y, Yin F, Liu J, Liu Z. Geniposide attenuates the phosphorylation of tau protein in cellular and insulin-deficient APP/PS1 transgenic mouse model of alzheimer’s disease. Chem Biol Drug Des 2016; 87(3): 409-18.
[http://dx.doi.org/10.1111/cbdd.12673] [PMID: 26475430]
[58]
Kellar D, Craft S. Brain insulin resistance in Alzheimer’s disease and related disorders: Mechanisms and therapeutic approaches. Lancet Neurol 2020; 19(9): 758-66.
[http://dx.doi.org/10.1016/S1474-4422(20)30231-3] [PMID: 32730766]
[59]
Walker JM, Dixit S, Saulsberry AC, May JM, Harrison FE. Reversal of high fat diet-induced obesity improves glucose tolerance, inflammatory response, β-amyloid accumulation and cognitive decline in the APP/PSEN1 mouse model of Alzheimer’s disease. Neurobiol Dis 2017; 100: 87-98.
[http://dx.doi.org/10.1016/j.nbd.2017.01.004] [PMID: 28108292]
[60]
Baufeld C, Osterloh A, Prokop S, Miller KR, Heppner FL. High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia. Acta Neuropathol 2016; 132(3): 361-75.
[http://dx.doi.org/10.1007/s00401-016-1595-4] [PMID: 27393312]
[61]
Medrano-Jiménez E, Jiménez-Ferrer Carrillo I, Pedraza-Escalona M, et al. Malva parviflora extract ameliorates the deleterious effects of a high fat diet on the cognitive deficit in a mouse model of Alzheimer’s disease by restoring microglial function via a PPAR-γ-dependent mechanism. J Neuroinflammation 2019; 16(1): 143.
[http://dx.doi.org/10.1186/s12974-019-1515-3] [PMID: 31291963]
[62]
Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ. Using mice to model Alzheimer’s dementia: An overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front Genet 2014; 5: 88.
[http://dx.doi.org/10.3389/fgene.2014.00088] [PMID: 24795750]
[63]
Xu J, Gao H, Zhang L, et al. Melatonin alleviates cognition impairment by antagonizing brain insulin resistance in aged rats fed a high-fat diet. J Pineal Res 2019; 67(2): e12584.
[http://dx.doi.org/10.1111/jpi.12584] [PMID: 31050371]
[64]
Barnes LL, Wilson RS, Bienias JL, Schneider JA, Evans DA, Bennett DA. Sex differences in the clinical manifestations of Alzheimer disease pathology. Arch Gen Psychiatry 2005; 62(6): 685-91.
[http://dx.doi.org/10.1001/archpsyc.62.6.685] [PMID: 15939846]
[65]
Chapman RM, Mapstone M, Gardner MN, et al. Women have farther to fall: Gender differences between normal elderly and Alzheimer’s disease in verbal memory engender better detection of Alzheimer’s disease in women. J Int Neuropsychol Soc 2011; 17(4): 654-62.
[http://dx.doi.org/10.1017/S1355617711000452] [PMID: 21486518]
[66]
Altmann A, Tian L, Henderson VW, Greicius MD. Sex modifies the APOE-related risk of developing Alzheimer disease. Ann Neurol 2014; 75(4): 563-73.
[http://dx.doi.org/10.1002/ana.24135] [PMID: 24623176]
[67]
Ungar L, Altmann A, Greicius MD. Apolipoprotein E, gender, and Alzheimer’s disease: An overlooked, but potent and promising interaction. Brain Imaging Behav 2014; 8(2): 262-73.
[http://dx.doi.org/10.1007/s11682-013-9272-x] [PMID: 24293121]
[68]
Hirata-Fukae C, Li HF, Hoe HS, et al. Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Brain Res 2008; 1216: 92-103.
[http://dx.doi.org/10.1016/j.brainres.2008.03.079] [PMID: 18486110]
[69]
Carroll JC, Rosario ER, Kreimer S, et al. Sex differences in β-amyloid accumulation in 3xTg-AD mice: Role of neonatal sex steroid hormone exposure. Brain Res 2010; 1366: 233-45.
[http://dx.doi.org/10.1016/j.brainres.2010.10.009] [PMID: 20934413]

Rights & Permissions Print Cite
Article Metrics
22
1
© 2024 Bentham Science Publishers | Privacy Policy