Abstract
It is reported that chitinase1 increases in Alzheimer’s disease (AD). However, the alteration of chitinase1 in the progress of AD is still unclear. Thus, we designed the present study to detect chitinase1 level in different stages of APP/PS1 double transgenic mice. Experimental models were APP/PS1 double transgenic mice with 4, 12 and 22 months. Cognitive function was detected by Morris water maze test in APP/PS1 mice as well as controls. ELISA and the quantitative RT-PCR were used to detect chitinase1 level in different groups. The study displayed that expression of chitinase1 gradually increased in a time-dependent manner in APP/PS1 mice, while there were no statistical differences among the wild-type mice in varies ages. Moreover, chitnase1 increased significantly in APP/PS1 mice aged 12 and 22 months compared with the age matched wild-type group, respectively. However, no difference of chitnase1 was found between 4 months-old APP/PS1 mice and wild-type mice. Comparing with the age matched wild type group, the consequences of mRNA on the increase in chitnase1 is in accordance with protein in APP/PS1 mice. Furthermore, Morris water maze showed that 4 months-old APP/PS1 mice have normal spatial learning and impaired spatial memory; both spatial learning and spatial memory in 12 and 22 months-old APP/PS1 mice were declined. Time-dependent increase of chitnase1 in APP/PS1 double transgenic mice indicates that the level of chitinase1 is associated with decline of cognition. Therefore, chitinase1 might be a biomarker of disease progression in AD.
Similar content being viewed by others
References
Qiu C, Kivipelto M, von Strauss E (2009) Epidemiology of Alzheimer’s disease: occurrence, determinants, and strategies toward intervention. Dialogues Clin Neurosci 11(2):111–128
Prince M, Wimo A. Guerchet M, Ali G (2015) Alzheimer’s disease international. world Alzheimer report 2015 the global impact of dementia an analysis of prevalence, incidence, cost and trends. Alzheimer’s Disease International, London. http://www.alz.co.uk/research/world-report-2015
Langa KM (2015) Is the risk of Alzheimer’s disease and dementia declining? Alzheimer’s Res Ther 7(1):34. doi:10.1186/s13195-015-0118-1
Noorbakhsh F, Overall CM, Power C (2009) Deciphering complex mechanisms in neurodegenerative diseases: the advent of systems biology. Trends Neurosci 32(2):88–100. doi:10.1016/j.tins.2008.10.003
Walter J, vanchten-Deckert G (2013) Cross-talk of membrane lipids and Alzheimer-related proteins. Mol Neurodegener 8:34. doi:10.1186/1750-1326-8-34
Ando K, Brion JP, Stygelbout V, Authelet M, Dedecker R, Chanut A, Lacor P, Lavaur J, Sazdovitch V, Rogaeva E, Potier MC, Duyckaerts C (2013) Clathrin adaptor CALM/PICALM is associated with neurofibrillary tangles and is cleaved in Alzheimer’s brains. Acta Neuropathol 125(6):861–878. doi:10.1007/s00401-013-1111-z
Santos RX, Correia SC, Zhu X, Smith MA, Moreira PI, Castellani RJ, Nunomura A, Perry G (2013) Mitochondrial DNA oxidative damage and repair in aging and Alzheimer’s disease. Antioxid Redox Signal 18(18):2444–2457. doi:10.1089/ars.2012.5039
Wolfe MS (2012) The role of tau in neurodegenerative diseases and its potential as a therapeutic target. Scientifica. doi:10.6064/2012/796024 (Cairo)
Blennow K, Hampel H, Weiner M, Zetterberg H (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 2010(6):131–144. doi:10.1038/nrneurol.2010.4
Hampel H, Prvulovic D, Teipel S, Jessen F, Luckhaus C, Frolich L, Riepe MW, Dodel R, Leyhe T, Bertram L, Hoffmann W, Faltraco F (2011) The future of Alzheimer’s disease: the next 10 years. German Task Force on Alzheimer’s Disease (GTF-AD). Prog Neurobiol 95(4):718–728. doi:10.1016/j.pneurobio.2011.11.008
Di Rosa M, Dell’Ombra N, Zambito AM, Malaguarnera M, Nicoletti F, Malaguarnera L (2006) Chitotriosidase and inflammatory mediator levels in Alzheimer’s disease and cerebrovascular dementia. Eur J Neurosci 23(10):2648–2656
Sotgiu S, Piras MR, Barone R, Arru G, Fois ML, Rosati G, Musumeci S (2007) Chitotriosidase and Alzheimer’s disease. Curr Alzheimer Res 4(3):295–296
Barone R, Sotgiu S, Musumeci S (2007) Plasma chitotriosidase in health and pathology. Clin Lab 53(5–6):321–333
Watabe-Rudolph M, Song Z, Lausser L, Schnack C, Begus-Nahrmann Y, Scheitharer MO, Rettinger G, Otto M, Tumani H, Thal DR, Arrems J, Jellinger KA, Kestler HA, von Arnim CA, Rudolph KL (2012) Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer disease. Neurology 78(8):569–577. doi:10.1212/WNL.0b013e318247caa1
Trinchese F, Liu S, Battaglia F, Walter S, Mathews PM, Arancio O (2004) Progressive age-related development of Alzheimer-like pathology in APP/PS1 mice. Ann Neurol 55:801–814
Zhao G, Liu HL, Zhang H, Tong XJ (2015) Treadmill exercise enhances synaptic plasticity, but does not alter beta-amyloid deposition in hippocampus of aged APP/PS1 transgenic mice. Neuroscience 298:357–366. doi:10.1080/16506073.2015.1012740
Flurkey K, Currer JM, Harrison DE (2007) The mouse in aging research. In: Fox JG et al (eds) The mouse in biomedical research, 2nd edn. American College Laboratory Animal Medicine (Elsevier), Burlington, MA, pp 637–672
The Jackson Laboratory (2012) Maximum lifespan as a biomarker of aging. http://research.jax.Org/faculty/Harrison/gerlvLifespanl.html
Zhang D, Hu X, Qian L, Qian L, Chen SH, Zhou H, Wilson B, Miller DS, Hong JS (2011) Microglial MAC1 receptor and PI3 K are essential in mediating β-amyloid peptide-induced microglial activation and subsequent neurotoxicity. J Neuroinflammation 8(1):3. doi:10.1186/1742-2094-8-3
Di Rosa M, Distefano G, Zorena K, Malaguarnera L (2016) Chitinases and immunity: ancestral molecules with new functions. Immunobiology 221(3):399–411. doi:10.1016/j.imbio.2015.11.014
Rathore AS, Gupta RD (2015) Chitinases from bacteria to human: properties, applications, and future perspectives. Enzyme Res. doi:10.1155/2015/791907
Bussink AP, Speijer D, Aerts JM, Boot RG (2007) Evolution of mammalian chitinase(-like) members of family 18 glycosyl hydrolases. Genetics 177:959–970
Hollak CE, Weely S, Oers MH, Aerts JM (1994) Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucherdisease. J Clin Invest 93:1288–1292
Hakala BE, White C (1993) Recklies AD Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J Biol Chem 268:25803–25810
Malmeström C, Axelsson M, Lycke J, Zetterberg H, Blennow K, Olsson B (2014) CSF levels of YKL-40 are increased in MS and replaces with immunosuppressive treatment. J Neuroimmunol 269(1–2):87–89. doi:10.1016/j.Jneuroim.2014.02.004
Mattsson N, Tabatabaei S, Johansson P, Hansson O, Andreasson U, Mansson JE, Johansson JO, Olsson B, Wallin A, Svensson J, Blennow K (2011) Zetterberg H Cerebrospinal fluid microglial markers in Alzheimer’s disease: elevated chitotriosidase activity but lack of diagnostic utility. Neuromolecular Med 13(2):151–159. doi:10.1007/s12017-011-8147-9
Craig-Schapiro R, Perrin Richard J, Roe Catherine M, Carter Chengjie Xiong Deborah, Cairns Nigel J, Mintun Mark A, Peskind Elaine R, Li Ge, Galasko Douglas R, Clark Christopher M, Quinn Joseph F, D’Angelo Gina, Malone James P, Reid Townsend R, Morris John C, Fagan Anne M, Holtzman David M (2010) YKL-40: a Novel Prognostic Fluid Biomarker for Preclinical Alzheimer’s Disease. Biol Psychiatry 68(10):903–912. doi:10.1016/j.biopsych.2010.08.025
Kanneganti M, Kamba A, Mizoguchi E (2012) Role of chitotriosidase (chitinase 1) under normal and disease conditions. J Epithel Biol Pharmacol 5:1–9
Elias JA, Homer RJ, Hamid Q, Lee CG (2005) Chitinases and chitinase-like proteins in T (H) 2 inflammation and asthma. J Allergy Clin Immunol 116(3):497–500
Sumarac Z, Suvajdzic N, Ignjatovic S, Majkic-Singh N, Janic D, Petakov M, Dordevic M, Mitrovic M, Dajak M, Golubovic M, Rodic P (2011) Biomarkers in Serbianpatients with Gaucher disease. Clin Biochem 44(12):950–954. doi:10.1016/j.clinbiochem.2011.05.016
Mattsson N, Tabatabaei S, Johansson P, Hansson O, AndreassonU Mansson J-E, Johansson J-O, Olsson B, Wallin A, Svensson J, Blennow K, Zetterberg H (2010) Cerebrospinalfluid microglial markers in Alzheimer’s disease: elevatedchitotriosidase activity but lack of diagnostic utility. Neuromolecular Med. doi:10.1007/s12017-011-8147-9
Blennow K, Hampel H (2003) CSF markers for incipient Alzheimer’s disease. Lancet Neurol 2:605–613. doi:10.1016/S1474-4422(03)00530-1
Jenny NS (2012) Inflammation in aging: cause, effect, or both? Discov Med 13(73):451–460
Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K, Frautschy SA, Finsen B, Brown GC, Verkhratsky A, Yamanaka K, Koistinaho J, Latz E, Halle A, Petzold GC, Town T, Morgan D, Shinohara ML, Perry VH, Holmes C, Bazan NG, Brooks DJ, Hunot S, Joseph B, Deigendesch N, Garaschuk O, Boddeke E, Dinarello CA, Breitner JC, Cole GM, Golenbock DT, Kummer MP (2015) Neuroinflammation in Alzheimer’s disease. Lancet Neurol 14(4):388–405. doi:10.1016/S1474-4422(15)70016-5
Olsson B, Hertze J, Lautner R, Zetterberg H, Nagga K, Hoglund K, Basun H, Annas P, Lannfelt L, Andreasen N, Minthon L, Blennow K, Hansson O (2013) Microglial markers are elevated in the prodromal phase of Alzheimer’s disease and vascular dementia. J Alzheimers Dis 33:45–53. doi:10.3233/JAD-2012-120787
Ji K, Akgul G, Wollmuth LP, Tsirka SE (2013) Microglia actively regulatethe number of functional synapses. PLoS One 8(2):e56293. doi:10.1371/journal.pone.0056293
Di Rosa M, Musumeci M, Scuto A, Musumeci S, Malaguarnera L (2005) Effect of interferon-gamma, interleukin 10, lipopolysaccharide and tumor necrosis factor-alpha on chitotriosidase synthesis in human macrophages. Clin Chem Lab Med 43:499–502
Sotgiu S, Barone R, Zanda B, Arru G, Fois ML, Arru A, Rosati G, Marchetti B, Musumeci S (2005) Chitotriosidase in patients with acute ischemic stroke. Eur Neurol 54(3):149–153
Boot RG, Renkema H, Strijland A, van Zonneveld AJ, Aerts JMFG (1995) Cloning of cDNA encoding chitotriosidase, a human chitinase produced by macrophages. J Biol Chem 270:26252–26256
Neniskyte U, Neher JJ, Brown GC (2011) Neuronal death induced by nanomolar amyloid beta is mediated by primary phagocytosis of neurons by microglia. J Biol Chem 286(46):39904–39913. doi:10.1074/jbc.M111.267583
Sotgiu S, Musumeci S, Marconi S, Gini B, Bonetti B (2008) Different content of chitin-like polysaccharides in multiple sclerosis and Alzheimer’s disease brains. J Neuroimmunol 197(1):70–73. doi:10.1016/j.jneuroim.2008.03.021
Castellani RJ, Siedlak SL, Fortino AE, Perry G, Ghetti B, Smith MA (2005) Chitin-like polysaccharides in Alzheimer’s disease brains [J]. Curr Alzheimer Res 2(4):419–423
Acknowledgments
This study is supported by grants from National Key Clinical Specialties Construction Program of China (No. [2013]544), and Application Program of Chongqing Science & Technology Commission (cstc2014yykfA110002). None of the authors declared a conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
Qian Xiao and Rui Shi have contributed equally to this work.
Rights and permissions
About this article
Cite this article
Xiao, Q., Shi, R., Yang, W. et al. Time-Dependent Increase of Chitinase1 in APP/PS1 Double Transgenic Mice. Neurochem Res 41, 1604–1611 (2016). https://doi.org/10.1007/s11064-016-1874-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-016-1874-4