Long-term icariin treatment ameliorates cognitive deficits via CD4⁺ T cell-mediated immuno-inflammatory responses in APP/PS1 mice

References

• Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer‘s disease. Nat Rev Dis Primers. 2015;1:15056. doi:10.1038/nrdp.2015.5627188934
   PubMed Web of Science ®Google Scholar
• Alzheimer‘s Disease International. World Alzheimer report 2018: the state of the art of dementia research: new frontiers. Available at: https://www.alz.co.uk/research/WorldAlzheimerReport2018.pdf. Accessed January, 2019.
   Google Scholar
• Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer‘s disease at 25 years. EMBO Mol Med. 2016;8:595–608. doi:10.15252/emmm.20160621027025652
   PubMed Web of Science ®Google Scholar
• Scheltens P, Blennow K, Breteler MM, et al. Alzheimer‘s disease. Lancet. 2016;388:505–517. doi:10.1016/S0140-6736(15)01124-126921134
   PubMed Web of Science ®Google Scholar
• Calsolaro V, Edison P. Neuroinflammation in Alzheimer‘s disease: current evidence and future directions. Alzheimers Dement. 2016;12:719–732. doi:10.1016/j.jalz.2016.02.01027179961
   PubMed Web of Science ®Google Scholar
• Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer‘s disease. Alzheimers Dement (NY). 2018;4:575–590. doi:10.1016/j.trci.2018.06.014
   PubMedGoogle Scholar
• Vom Berg J, Prokop S, Miller KR, et al. Inhibition of IL-12/IL-23 signaling reduces Alzheimer‘s disease-like pathology and cognitive decline. Nat Med. 2012;18:1812–1819. doi:10.1038/nm.296523178247
   PubMed Web of Science ®Google Scholar
• Heneka MT, Kummer MP, Stutz A, et al. NLRP3 is activated in Alzheimer‘s disease and contributes to pathology in APP/PS1 mice. Nature. 2013;493:674–678. doi:10.1038/nature1172923254930
   PubMed Web of Science ®Google Scholar
• Rogers J, Luber-Narod J, Styren SD, Civin WH. Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer‘s disease. Neurobiol Aging. 1988;9:339–349.3263583
   PubMed Web of Science ®Google Scholar
• McManus RM, Mills KH, Lynch MA. T cells-protective or pathogenic in Alzheimer‘s disease? J Neuroimmune Pharmacol. 2015;10:547–560. doi:10.1007/s11481-015-9612-225957956
   PubMed Web of Science ®Google Scholar
• Kivisakk P, Mahad DJ, Callahan MK, et al. Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin. Proc Natl Acad Sci U S A. 2003;100:8389–8394. doi:10.1073/pnas.143300010012829791
   PubMed Web of Science ®Google Scholar
• Monsonego A, Nemirovsky A, Harpaz I. CD4 T cells in immunity and immunotherapy of Alzheimer‘s disease. Immunology. 2013;139:438–446. doi:10.1111/imm.1210323534386
   PubMed Web of Science ®Google Scholar
• Wolf SA, Steiner B, Akpinarli A, et al. CD4-positive T lymphocytes provide a neuroimmunological link in the control of adult hippocampal neurogenesis. J Immunol. 2009;182:3979–3984. doi:10.4049/jimmunol.080121819299695
   PubMed Web of Science ®Google Scholar
• Dansokho C, Ait Ahmed D, Aid S, et al. Regulatory T cells delay disease progression in Alzheimer-like pathology. Brain. 2016;139:1237–1251. doi:10.1093/brain/awv40826912648
   PubMed Web of Science ®Google Scholar
• He Y, Li H, Zhang F, et al. Immunotherapeutic effects of lymphocytes co-cultured with human cord blood-derived multipotent stem cells transplantation on APP/PS1 mice. Behav Brain Res. 2016;315:94–102. doi:10.1016/j.bbr.2016.08.02527528555
   PubMed Web of Science ®Google Scholar
• Xu CQ, Liu BJ, Wu JF, et al. Icariin attenuates LPS-induced acute inflammatory responses: involvement of PI3K/Akt and NF-kappaB signaling pathway. Eur J Pharmacol. 2010;642:146–153. doi:10.1016/j.ejphar.2010.05.01220519138
   PubMed Web of Science ®Google Scholar
• Liu L, Zhao Z, Lu L, et al. Icariin and icaritin ameliorated hippocampus neuroinflammation via inhibiting HMGB1-related pro-inflammatory signals in lipopolysaccharide-induced inflammation model in C57BL/6J mice. Int Immunopharmacol. 2019;68:95–105. doi:10.1016/j.intimp.2018.12.05530616172
   PubMed Web of Science ®Google Scholar
• He XL, Zhou WQ, Bi MG, Du G-H. Neuroprotective effects of icariin on memory impairment and neurochemical deficits in senescence-accelerated mouse prone 8 (SAMP8) mice. Brain Res. 2010;1334:73–83. doi:10.1016/j.brainres.2010.03.08420380820
   PubMed Web of Science ®Google Scholar
• Jin F, Gong QH, Xu YS, et al. Icariin, a phosphodiesterase-5 inhibitor, improves learning and memory in APP/PS1 transgenic mice by stimulation of NO/cGMP signalling. Int J Neuropsychopharmacol. 2014;17:871–881. doi:10.1017/S146114571300153324513083
   PubMed Web of Science ®Google Scholar
• Li F, Dong HX, Gong QH, Wu Q, Jin F, Shi JS. Icariin decreases both APP and Abeta levels and increases neurogenesis in the brain of Tg2576 mice. Neuroscience. 2015;304:29–35. doi:10.1016/j.neuroscience.2015.06.01026079110
   PubMed Web of Science ®Google Scholar
• Tao F, Qian C, Guo W, Luo Q, Xu Q, Sun Y. Inhibition of Th1/Th17 responses via suppression of STAT1 and STAT3 activation contributes to the amelioration of murine experimental colitis by a natural flavonoid glucoside icariin. Biochem Pharmacol. 2013;85:798–807. doi:10.1016/j.bcp.2012.12.00223261528
   PubMed Web of Science ®Google Scholar
• Li X, Hu Y, He L, et al. Icaritin inhibits T cell activation and prolongs skin allograft survival in mice. Int Immunopharmacol. 2012;13:1–7. doi:10.1016/j.intimp.2012.02.01122406176
   PubMed Web of Science ®Google Scholar
• Wei Y, Liu B, Sun J, et al. Regulation of Th17/Treg function contributes to the attenuation of chronic airway inflammation by icariin in ovalbumin-induced murine asthma model. Immunobiology. 2015;220:789–797. doi:10.1016/j.imbio.2014.12.01525613226
   PubMed Web of Science ®Google Scholar
• Li X, Bao X, Wang R. Experimental models of Alzheimer‘s disease for deciphering the pathogenesis and therapeutic screening (Review). Int J Mol Med. 2016;37:271–283. doi:10.3892/ijmm.2015.242826676932
   PubMed Web of Science ®Google Scholar
• Holcomb L, Gordon MN, McGowan E, et al. Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med. 1998;4:97–100.9427614
   PubMed Web of Science ®Google Scholar
• Imbimbo BP, Giardino L, Sivilia S, et al. CHF5074, a novel gamma-secretase modulator, restores hippocampal neurogenesis potential and reverses contextual memory deficit in a transgenic mouse model of Alzheimer‘s disease. J Alzheimers Dis. 2010;20:159–173. doi:10.3233/JAD-2010-136620164581
   PubMed Web of Science ®Google Scholar
• Schluesener JK, Schluesener H. Plant polyphenols in the treatment of age-associated diseases: revealing the pleiotropic effects of icariin by network analysis. Mol Nutr Food Res. 2014;58:49–60. doi:10.1002/mnfr.20130040924311544
   PubMed Web of Science ®Google Scholar
• Zhang Y, Liu M, Sun H, Yin K. Matrine improves cognitive impairment and modulates the balance of Th17/Treg cytokines in a rat model of Abeta1-42-induced Alzheimer‘s disease. Cent Eur J Immunol. 2015;40:411–419. doi:10.5114/ceji.2015.5696126862304
   PubMed Web of Science ®Google Scholar
• Laurent C, Dorothee G, Hunot S, et al. Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of tauopathy. Brain. 2017;140:184–200. doi:10.1093/brain/aww27027818384
   PubMed Web of Science ®Google Scholar
• de Souza Tavares W, Akhtar Y, Goncalves GL, et al. Turmeric powder and its derivatives from Curcuma longa rhizomes: insecticidal effects on cabbage looper and the role of synergists. Sci Rep. 2016;6:34093. doi:10.1038/srep3409327804972
   PubMed Web of Science ®Google Scholar
• Gunathilake K, Rupasinghe H. Recent perspectives on the medicinal potential of ginger. Botanics. 2015;5:55–63.
   Google Scholar
• Moussa C, Hebron M, Huang X, et al. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer‘s disease. J Neuroinflammation. 2017;14:1. doi:10.1186/s12974-016-0779-028086917
   PubMed Web of Science ®Google Scholar
• Shen R, Deng W, Li C, Zeng G. A natural flavonoid glucoside icariin inhibits Th1 and Th17 cell differentiation and ameliorates experimental autoimmune encephalomyelitis. Int Immunopharmacol. 2015;24:224–231. doi:10.1016/j.intimp.2014.12.01525528476
   PubMed Web of Science ®Google Scholar
• Uddin MS, Stachowiak A, Mamun AA, et al. Autophagy and Alzheimer‘s disease: from molecular mechanisms to therapeutic implications. Front Aging Neurosci. 2018;10:04. doi:10.3389/fnagi.2018.0000429441009
   PubMed Web of Science ®Google Scholar
• Choi SH, Bylykbashi E, Chatila ZK, et al. Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer‘s mouse model. Science. 2018;361:eaan8821. doi:10.1126/science.aan882130190379
   PubMed Web of Science ®Google Scholar
• Gajera CR, Emich H, Lioubinski O, et al. LRP2 in ependymal cells regulates BMP signaling in the adult neurogenic niche. J Cell Sci. 2010;123:1922–1930. doi:10.1242/jcs.06591220460439
   PubMed Web of Science ®Google Scholar
• Kur E, Christa A, Veth KN, et al. Loss of Lrp2 in zebrafish disrupts pronephric tubular clearance but not forebrain development. Dev Dyn. 2011;240:1567–1577. doi:10.1002/dvdy.2262421455927
   PubMed Web of Science ®Google Scholar
• Tonnies E, Trushina E. Oxidative stress, synaptic dysfunction, and Alzheimer‘s disease. J Alzheimers Dis. 2017;57:1105–1121. doi:10.3233/JAD-16108828059794
   PubMed Web of Science ®Google Scholar
• Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 2011;1:a006189. doi:10.1101/cshperspect.a00618922229116
   PubMed Web of Science ®Google Scholar
• Gajera CR, Fernandez R, Postupna N, et al. Mass synaptometry: high-dimensional multi parametric assay for single synapses. J Neurosci Methods. 2019;312:73–83. doi:10.1016/j.jneumeth.2018.11.00830465796
   PubMed Web of Science ®Google Scholar
• Grinan-Ferre C, Corpas R, Puigoriol-Illamola D, et al. Understanding epigenetics in the neurodegeneration of Alzheimer‘s disease: SAMP8 mouse model. J Alzheimers Dis. 2018;62:943–963. doi:10.3233/JAD-17066429562529
   PubMed Web of Science ®Google Scholar
• Spitzer MH, Nolan GP. Mass cytometry: single cells, many features. Cell. 2016;165:780–791. doi:10.1016/j.cell.2016.04.01927153492
   PubMed Web of Science ®Google Scholar