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Aging and disease    2017, Vol. 8 Issue (1) : 101-114     DOI: 10.14336/AD.2016.0522
Original Article |
LW-AFC Effects on N-glycan Profile in Senescence-Accelerated Mouse Prone 8 Strain, a Mouse Model of Alzheimer’s Disease
Wang Jianhui1,2, Cheng Xiaorui1,2,*, Zeng Ju1,2, Yuan Jiangbei3, Wang Zhongfu3, Zhou Wenxia1,2,*, Zhang Yongxiang1,2
1Department of TCM and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
2State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China
3Educational Ministry Key Laboratory of Resource Biology and Biotechnology in Western China, Life Sciences College, Northwest University, Xi’an 710069, China
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Glycosylation is one of the most common eukaryotic post-translational modifications, and aberrant glycosylation has been linked to many diseases. However, glycosylation and glycome analysis is a significantly challenging task. Although several lines of evidence have indicated that protein glycosylation is defective in Alzheimer’s disease (AD), only a few studies have focused on AD glycomics. The etiology of AD is unclear and there are no effective disease-modifying treatments for AD. In this study, we found that the object recognition memory, passive avoidance, and spatial learning and memory of senescence-accelerated mouse prone 8 (SAMP8) strain, an AD animal model, were deficient, and LW-AFC, which was prepared from the traditional Chinese medicine prescription Liuwei Dihuang decoction, showed beneficial effects on the deterioration of cognitive capability in SAMP8 mice. Forty-three and 56 N-glycan were identified in the cerebral cortex and serum of SAMP8 mice, respectively. The N-glycan profile in SAMP8 mice was significantly different from that of senescence accelerated mouse resistant 1 (SAMR1) strains, the control of SAMP8 mice. Treatment with LW-AFC modulated the abundance of 21 and 6 N-glycan in the cerebral cortex and serum of SAMP8 mice, respectively. The abundance of (Hex)3(HexNAc)5(Fuc)1(Neu5Ac)1 and (Hex)2(HexNAc)4 decreased in the cerebral cortex and serum of SAMP8 mice compared with SAMR1 mice, decreases that were significantly correlated with learning and memory measures. The administration of LW-AFC could reverse or increase these levels in SAMP8 mice. These results indicated that the effects of LW-AFC on cognitive impairments in SAMP8 mice might be through modulation of N-glycan patterns, and LW-AFC may be a potential anti-AD agent.

Keywords LW-AFC      traditional Chinese medicine      glycome      senescence-accelerated mouse prone 8 strain      Alzheimer’s disease     
Corresponding Authors: Cheng Xiaorui,Zhou Wenxia   
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Co-first author, these two authors contributed equally to this work.

Issue Date: 01 February 2017
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Wang Jianhui
Cheng Xiaorui
Zeng Ju
Yuan Jiangbei
Wang Zhongfu
Zhou Wenxia
Zhang Yongxiang
Cite this article:   
Wang Jianhui,Cheng Xiaorui,Zeng Ju, et al. LW-AFC Effects on N-glycan Profile in Senescence-Accelerated Mouse Prone 8 Strain, a Mouse Model of Alzheimer’s Disease[J]. Aging and disease, 2017, 8(1): 101-114.
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Figure 1.  The treatment of LW-AFC ameliorated cognitive deterioration of SAMP8 mice. The discrimination index (A) in the object recognition memory test. The latency in the short-term (B) and long term (C) passive avoidance test respectively in step-down test. The escape latency (D) in Morris water maze test. The time in the target quadrant (E) and the number of crossing platform (F) in the probe trial of Morris water maze test. *p < 0.05, ***p < 0.001, comparing with SAMR1 mice. #p < 0.05, ###p < 0.001, comparing with SAMP8 mice. Mean or mean ± S.D., n=3, Student’s t-test.
No.Observed mass(m/z)TypeProposed compositionRelative abundance in SAMR1groupRelative abundance in SAMP8 groupRelative abundance in SAMP8+LW-AFC group
Table 1  The effect of LW-AFC on N-glycan profile in the cerebral cortex of SAMP8 mice
Figure 2.  The effect of LW-AFC on N-glycan in the cerebral cortex of SAMP8 mice. **p<0.01, comparing with SAMR1 mice. #p<0.05, comparing with SAMP8 mice. Mean ± S.D., n=3, Student’s t-test.
Figure 3.  Correlation between relative abundance of (Hex)3(HexNAc)5(Fuc)1(Neu5Ac)1 in cerebral cortex and ability of learning and memory of SAM mice. n=8-9, two-tailed Pearson analysis, confidence interval 95%.
NoObserved mass (m/z)TypeProposed compositionRelative abundance in SAMR1groupRelative abundance in SAMP8 groupRelative abundance in SAMP8+LW-AFC group
Table 2  The effect of LW-AFC on N-glycan profile in the serum of SAMP8 mice
Figure 4.  The effect of LW-AFC on N-glycan in the serum of SAMP8 mice. *p<0.05, comparing with SAMR1 mice. #p<0.05, comparing with SAMP8 mice. Mean ± S.D., n=3, Student’s t-test.
Figure 5.  Correlation between relative abundance of (Hex)2(HexNAc)4 in serum and ability of learning and memory of SAM mice. n=9, two-tailed Pearson analysis, confidence interval 95%.
[1] Goyallon A, Cholet S, Chapelle M, Junot C, Fenaille F (2015). Evaluation of a combined glycomics and glycoproteomics approach for studying the major glycoproteins present in biofluids: Application to cerebrospinal fluid. Rapid Commun Mass Sp, 29(6):461-473.
[2] Zerze GH, Mittal J (2015). Effect of O-linked glycosylation on the equilibrium structural ensemble of intrinsically disordered polypeptides. J Phys Chem B, 119(51):15583-15592.
[3] Saito F, Yanagisawa K, Miyatake T (1993). Soluble derivatives of beta/A4 amyloid protein precursor in human cerebrospinal fluid are both N- and O-glycosylated. Brain Res Mol Brain Res, 19(1-2):171-174.
[4] Pahlsson P, Spitalnik SL (1996). The role of glycosylation in synthesis and secretion of beta-amyloid precursor protein by Chinese hamster ovary cells. Arch Biochem Biophys, 331(2):177-186.
[5] Sato Y, Liu C, Wojczyk BS, Kobata A, Spitalnik SL, Endo T (1999). Study of the sugar chains of recombinant human amyloid precursor protein produced by Chinese hamster ovary cells. Bba-Gen Subjects, 1472(1-2):344-358.
[6] Akasaka-Manya K, Manya H, Sakurai Y, Wojczyk BS, Kozutsumi Y, Saito Y, et al. (2010). Protective effect of N-glycan bisecting GlcNAc residues on beta-amyloid production in Alzheimer’s disease. Glycobiology, 20(1):99-106.
[7] Halim A, Brinkmalm G, Ruetschi U, Westman-Brinkmalm A, Portelius E, Zetterberg H, et al. (2011). Site-specific characterization of threonine, serine, and tyrosine glycosylations of amyloid precursor protein/amyloid beta-peptides in human cerebrospinal fluid. Proc Natl Acad Sci U S A, 108(29):11848-11853.
[8] Vanoni O, Paganetti P, Molinari M (2008). Consequences of individual N-glycan deletions and of proteasomal inhibition on secretion of active BACE. Mol Biol Cell, 19(10):4086-4098.
[9] Wang JZ, Grundke-Iqbal I, Iqbal K (1996). Glycosylation of microtubule-associated protein tau: An abnormal posttranslational modification in Alzheimer’s disease. Nat Med, 2(8):871-875.
[10] Takahashi M, Tsujioka Y, Yamada T, Tsuboi Y, Okada H, Yamamoto T, et al. (1999). Glycosylation of microtubule-associated protein tau in Alzheimer’s disease brain. Acta Neuropathol, 97(6):635-641.
[11] Sato Y, Naito Y, Grundke-Iqbal I, Iqbal K, Endo T (2001). Analysis of N-glycans of pathological tau: possible occurrence of aberrant processing of tau in Alzheimer’s disease. Febs Lett, 496(2-3):152-160.
[12] Chen VP, Choi RCY, Chan WKB, Leung KW, Guo AJY, Chan GKL, et al. (2011). The assembly of proline-rich membrane anchor (PRiMA)-linked acetylcholinesterase enzyme glycosylation is required for enzymatic activity but not for oligomerization. J Biol Chem. 2011; 286(38):32948-32961.
[13] Luk WKW, Chen VP, Choi RCY, Tsim KWK (2012). N-linked glycosylation of dimeric acetylcholinesterase in erythrocytes is essential for enzyme maturation and membrane targeting. Febs J, 279(17):3229-3239.
[14] Van Rensburg SJ, Berman P, Potocnik F, MacGregor P, Hon D, de Villiers N (2004). 5-and 6-glycosylation of transferrin in patients with Alzheimer’s disease. Metab Brain Dis, 19(1-2):89-96.
[15] Futakawa S, Nara K, Miyajima M, Kuno A, Ito H, Kaji H, et al. (2012). A unique N-glycan on human transferrin in CSF: a possible biomarker for iNPH. Neurobiol Aging, 33(8):1807-1815.
[16] Schedin-Weiss S, Winblad B, Tjernberg LO (2014). The role of protein glycosylation in Alzheimer disease. Febs J, 281(1):46-62.
[17] Rowlands D, Sugahara K, Kwok JCF (2015). Glycosaminoglycans and glycomimetics in the central nervous system. Molecules, 20(3):3527-3548.
[18] Xu ML, Luk WKW, Lau KM, Bi CWC, Cheng AWM, Gong AGW, et al. (2015). Three N-glycosylation sites of human acetylcholinesterase shares similar glycan composition. J Mol Neurosci, 57(4):486-491.
[19] Palmigiano A, Barone R, Sturiale L, Sanfilippo C, Bua RO, Romeo DA, et al. (2016). CSF N-glycoproteomics for early diagnosis in Alzheimer’s disease. J Proteomics, 131:29-37.
[20] Chen CC, Engelborghs S, Dewaele S, Le Bastard N, Martin JJ, Vanhooren V, et al. (2010). Altered serum glycomics in Alzheimer disease: a potential blood biomarker? Rejuvenation Res, 13(4):439-444.
[21] Ianni M, Manerba M, Di Stefano G, Porcellini E, Chiappelli M, Carbone I, et al. (2010) Altered glycosylation profile of purified plasma ACT from Alzheimer’s disease. Immun Ageing, 7 Suppl 1:S6.
[22] Lundstrom SL, Yang HQ, Lyutvinskiy Y, Rutishauser D, Herukka SK, Soininen H, et al. (2014). Blood plasma IgG Fc glycans are significantly altered in Alzheimer’s disease and progressive mild cognitive impairment. J Alzheimers Dis, 38(3):567-579.
[23] Gizaw ST, Ohashi T, Tanaka M, Hinou H, Nishimura SI (2016). Glycoblotting method allows for rapid and efficient glycome profiling of human Alzheimer’s disease brain, serum and cerebrospinal fluid towards potential biomarker discovery. Biochim Biophys Acta.
[24] Pallas M, Camins A, Smith MA, Perry G, Lee HG, Casadesus G (2008). From aging to Alzheimer’s disease: unveiling "the switch" with the senescence-accelerated mouse model (SAMP8). J Alzheimer’s Dis, 15(4):615-624.
[25] Flood JF, Morley JE (1998). Learning and memory in the SAMP8 mouse. Neurosci Biobehav Rev, 22(1):1-20.
[26] Flood JF, Harris FJ, Morley JE (1996). Age-related changes in hippocampal drug facilitation of memory processing in SAMP8 mice. Neurobiol Aging, 17(1):15-24.
[27] Sawano E, Negishi T, Aoki T, Murakami M, Tashiro T (2013). Alterations in local thyroid hormone signaling in the hippocampus of the SAMP8 mouse at younger ages: Association with delayed myelination and behavioral abnormalities. J Neurosci Res, 91(3):382-392.
[28] Chiba Y, Shimada A, Kumagai N, Yoshikawa K, Ishii S, Furukawa A, et al. (2009). The senescence-accelerated mouse (SAM): a higher oxidative stress and age-dependent degenerative diseases model. Neurochem Res, 34(4):679-687.
[29] Morley JE, Armbrecht HJ, Farr SA, Kumar VB (2012). The senescence accelerated mouse (SAMP8) as a model for oxidative stress and Alzheimer’s disease. Biochim Biophys Acta. 1822(5):650-656.
[30] Tomobe K, Nomura Y (2009). Neurochemistry, neuropathology, and heredity in SAMP8: a mouse model of senescence. Neurochem Res, 34(4):660-669.
[31] Pallàs M (2012). Senescence-Accelerated Mice P8: a tool to study brain aging and Alzheimer’s disease in a mouse model. ISRN Cell Biology, 2012:1-12.
[32] Cheng XR, Zhou WX, Zhang YX (2014). The behavioral, pathological and therapeutic features of the senescence-accelerated mouse prone 8 strain as an Alzheimer’s disease animal model. Ageing Res Rev, 13:13-37.
[33] Yang Y, Cheng XR, Zhang GR, Zhou WX, Zhang YX (2012). Autocrine motility factor receptor is involved in the process of learning and memory in the central nervous system. Behav Brain Res, 229(2):412-418.
[34] Zhang GR, Cheng XR, Zhou WX, Zhang YX (2009). Age-related expression of calcium/calmodulin-dependent protein kinase II A in the hippocampus and cerebral cortex of senescence accelerated mouse prone/8 mice is modulated by anti-Alzheimer’s disease drugs. Neuroscience, 159(1):308-315.
[35] Zhang GR, Cheng XR, Zhou WX, Zhang YX (2008). Age-related expression of STUB1 in senescence-accelerated mice and its response to anti-Alzheimer’s disease traditional Chinese medicine. Neurosci Lett, 438(3):371-375.
[36] Cheng XR, Zhou WX, Zhang YX (2007). The effects of Liuwei Dihuang decoction on the gene expression in the hippocampus of senescence-accelerated mouse. Fitoterapia, 78(3):175-181.
[37] Yu J, Schorlemer M, Gomez Toledo A, Pett C, Sihlbom C, Larson G, et al. (2016). Distinctive MS/MS fragmentation pathways of glycopeptide-generated oxonium ions provide evidence of the glycan structure. Chemistry, 22(3):1114-1124.
[38] Bevins RA and Besheer J (2006). Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study ’recognition memory’. Nat Protoc, 1(3):1306-1311.
[39] Xu Y, Cheng X, Cui X, Wang T, Liu G, Yang R, et al. (2015). Effects of 5-h multimodal stress on the molecules and pathways involved in dendritic morphology and cognitive function. Neurobiol Learn Mem, 123:225-238.
[40] Vorhees CV and Williams MT (2006). Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc, 1(2):848-858.
[41] Hu ZY, Liu G, Cheng XR, Huang Y, Yang S, Qiao SY, et al. (2012). JD-30, an active fraction extracted from Danggui-Shaoyao-San, decreases beta-amyloid content and deposition, improves LTP reduction and prevents spatial cognition impairment in SAMP8 mice. Exp Gerontol, 47(1):14-22.
[42] He XL, Zhou WQ, Bi MG, Du GH (2010). Neuroprotective effects of icariin on memory impairment and neurochemical deficits in senescence-accelerated mouse prone 8 (SAMP8) mice. Brain Res, 1334:73-83.
[43] Lou G, Zhang Q, Xiao F, Xiang Q, Su Z, Zhang L, et al. (2012). Intranasal administration of TAT-haFGF((1)(4)(-)(1)(5)(4)) attenuates disease progression in a mouse model of Alzheimer’s disease. Neuroscience, 223:225-237.
[44] Shi YQ, Huang TW, Chen LM, Pan XD, Zhang J, Zhu YG, et al. (2010). Ginsenoside Rg1 attenuates amyloid-beta content, regulates PKA/CREB activity, and improves cognitive performance in SAMP8 mice. J Alzheimers Dis, 19(3):977-989.
[45] Cooper CA, Packer NH, Redmond JW (1994) The elimination of O-linked glycans from glycoproteins under non-reducing conditions. Glycoconj J, 11(2):163-167.
[46] Wang CJ, Fan WC, Zhang P, Wang ZF, Huang LJ (2011). One-pot nonreductive O-glycan release and labeling with 1-phenyl-3-methyl-5-pyrazolone followed by ESI-MS analysis. Proteomics, 11(21):4229-4242.
[47] Wang HM, Zhang P, Huang LJ, Wang ZF (2009). Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) application in carbohydrate analysis. Prog Chem, 21(6):1335-1343.
[48] Brooks SA, Carter TM, Royle L, Harvey DJ, Fry SA, Kinch C, et al. (2008). Altered glycosylation of proteins in cancer: what is the potential for new anti-tumour strategies. Anticancer Agents Med Chem, 8(1):2-21.
[49] Wahrenbrock MG, Varki A (2006). Multiple hepatic receptors cooperate to eliminate secretory mucins aberrantly entering the bloodstream: are circulating cancer mucins the "tip of the iceberg"? Cancer Res, 66(4):2433-2441.
[50] Ohtsubo K, Marth JD (2006). Glycosylation in cellular mechanisms of health and disease. Cell, 126(5):855-867.
[51] Rudd PM, Wormald MR, Dwek RA (2004). Sugar-mediated ligand-receptor interactions in the immune system. Trends Biotechnol, 22(10):524-530.
[52] Roseman S (2001). Reflections on glycobiology. J Biol Chem, 276(45):41527-41542.
[53] Lis H, Sharon N (1993). Protein glycosylation. Structural and functional aspects. Eur J Biochem, 218(1):1-27.
[54] Van der Zwaag B, Franke L, Poot M, Hochstenbach R, Spierenburg HA, Vorstman JA, et al. (2009). Gene-network analysis identifies susceptibility genes related to glycobiology in autism. PLoS One, 4(5):e5324.
[55] Miura Y, Endo T (2016). Glycomics and glycoproteomics focused on aging and age-related diseases - Glycans as a potential biomarker for physiological alterations. Biochim Biophys Acta.
[56] Liu L, Yan B, Huang J, Gu Q, Wang L, Fang M, et al. (2013). The identification and characterization of novel N-glycan-based biomarkers in gastric cancer. PLoS One, 8(10):e77821.
[57] Copeland RJ, Han G, Hart GW (2013). O-GlcNAcomics--revealing roles of O-GlcNAcylation in disease mechanisms and development of potential diagnostics. Proteomics Clin Appl, 7(9-10):597-606.
[58] Butterfield DA, Owen JB (2011). Lectin-affinity chromatography brain glycoproteomics and Alzheimer disease: insights into protein alterations consistent with the pathology and progression of this dementing disorder. Proteomics Clin Appl, 5(1-2):50-56.
[59] Gizaw ST, Koda T, Amano M, Kamimura K, Ohashi T, Hinou H, et al. (2015). A comprehensive glycome profiling of Huntington’s disease transgenic mice. Bba-Gen Subjects, 1850(9):1704-1718.
[60] Krasnewich D (2014). Human glycosylation disorders. Cancer Biomark, 14(1):3-16.
[61] Wang B (2012). Molecular mechanism underlying sialic acid as an essential nutrient for brain development and cognition. Adv Nutr, 3(3):465S-472S.
[62] Yoo SW, Motari MG, Susuki K, Prendergast J, Mountney A, Hurtado A, et al. (2015). Sialylation regulates brain structure and function. FASEB J, 29(7):3040-3053.
[63] Telford JE, Bones J, McManus C, Saldova R, Manning G, Doherty M, et al. (2012). Antipsychotic treatment of acute paranoid schizophrenia patients with olanzapine results in altered glycosylation of serum glycoproteins. J Proteome Res, 11(7):3743-3752.
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