Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2019

Open Access 01-12-2019 | Alzheimer's Disease | Research

Adiponectin suppresses amyloid-β oligomer (AβO)-induced inflammatory response of microglia via AdipoR1-AMPK-NF-κB signaling pathway

Authors: Min Jian, Jason Shing-Cheong Kwan, Myriam Bunting, Roy Chun-Laam Ng, Koon Ho Chan

Published in: Journal of Neuroinflammation | Issue 1/2019

Login to get access

Abstract

Background

Microglia-mediated neuroinflammation is important in Alzheimer’s disease (AD) pathogenesis. Extracellular deposition of β-amyloid (Aβ), a major pathological hallmark of AD, can induce microglia activation. Adiponectin (APN), an adipocyte-derived adipokine, exerts anti-inflammatory effects in the periphery and brain. Chronic APN deficiency leads to cognitive impairment and AD-like pathologies in aged mice. Here, we aim to study the role of APN in regulating microglia-mediated neuroinflammation in AD.

Methods

Inflammatory response of cultured microglia (BV2 cells) to AβO and effects of APN were studied by measuring levels of proinflammatory cytokines (tumor necrosis factor α [TNFα] and interleukin-1β [IL-1β]) in cultured medium before and after exposure to AβO, with and without APN pretreatment. Adiponectin receptor 1 (AdipoR1) and receptor 2 (AdipoR2) were targeted by small interference RNA. To study the neuroprotective effect of APN, cultured HT-22 hippocampal cells were treated with conditioned medium of AβO-exposed BV2 cells or were co-cultured with BV2 cells in transwells. The cytotoxicity of HT-22 hippocampal cells was assessed by MTT reduction. We generated APN-deficient AD mice (APN−/−5xFAD) by crossing APN-knockout mice with 5xFAD mice to determine the effects of APN deficiency on microglia-mediated neuroinflammation in AD.

Results

AdipoR1 and AdipoR2 were expressed in BV2 cells and microglia of mice. Pretreatment with APN for 2 h suppressed TNFα and IL-1β release induced by AβO in BV2 cells. Additionally, APN rescued the decrease of AMPK phosphorylation and suppressed nuclear translocation of nuclear factor kappa B (NF-κB) induced by AβO. Compound C, an inhibitor of AMPK, abolished these effects of APN. Knockdown of AdipoR1, but not AdipoR2 in BV2 cells, inhibited the ability of APN to suppress proinflammatory cytokine release induced by AβO. Moreover, pretreatment with APN inhibited the cytotoxicity of HT-22 cells co-cultured with AβO-exposed BV2 cells. Lastly, APN deficiency exacerbated microglia activation in 9-month-old APN−/−5xFAD mice associated with upregulation of TNFα and IL-1β in the cortex and hippocampus.

Conclusions

Our findings demonstrate that APN inhibits inflammatory response of microglia to AβO via AdipoR1-AMPK-NF-κB signaling, and APN deficiency aggravates microglia activation and neuroinflammation in AD mice. APN may be a novel therapeutic agent for inhibiting neuroinflammation in AD.
Appendix
Available only for authorised users
Literature
1.
Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S, Van der Flier WM. Alzheimer’s disease. Lancet. 2016;388:505–17.PubMedCrossRef
2.
3.
Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science. 1992;256:184–5.PubMedCrossRef
4.
Goure WF, Krafft GA, Jerecic J, Hefti F. Targeting the proper amyloid-beta neuronal toxins: a path forward for Alzheimer’s disease immunotherapeutics. Alzheimers Res Ther. 2014;6:42.PubMedPubMedCentralCrossRef
5.
6.
Hardy J. Alzheimer’s disease: the amyloid cascade hypothesis: an update and reappraisal. J Alzheimers Dis. 2006;9:151–3.PubMedCrossRef
7.
Li S, Jin M, Koeglsperger T, Shepardson NE, Shankar GM, Selkoe DJ. Soluble Abeta oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors. J Neurosci. 2011;31:6627–38.PubMedPubMedCentralCrossRef
8.
Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, et al. Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med. 2008;14:837–42.PubMedPubMedCentralCrossRef
9.
Forloni G, Artuso V, La Vitola P, Balducci C. Oligomeropathies and pathogenesis of Alzheimer and Parkinson’s diseases. Mov Disord. 2016;31:771–81.PubMedCrossRef
10.
Minter MR, Main BS, Brody KM, Zhang M, Taylor JM, Crack PJ. Soluble amyloid triggers a myeloid differentiation factor 88 and interferon regulatory factor 7 dependent neuronal type-1 interferon response in vitro. J Neuroinflammation. 2015;12:71.PubMedPubMedCentralCrossRef
11.
12.
Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, et al. TREM2 variants in Alzheimer’s disease. N Engl J Med. 2013;368:117–27.PubMedCrossRef
13.
Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14:388–405.PubMedPubMedCentralCrossRef
14.
Hickman SE, Allison EK, El Khoury J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J Neurosci. 2008;28:8354–60.PubMedPubMedCentralCrossRef
15.
Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007;10:1387–94.PubMedCrossRef
16.
Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR 3rd, Lafaille JJ, Hempstead BL, Littman DR, Gan WB. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell. 2013;155:1596–609.PubMedPubMedCentralCrossRef
17.
Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, Jones T, Banati RB. In-vivo measurement of activated microglia in dementia. Lancet. 2001;358:461–7.PubMedCrossRef
18.
Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, Ulland TK, David E, Baruch K, Lara-Astaiso D, Toth B, et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell. 2017;169:1276–1290 e1217.PubMedCrossRef
19.
Yamamoto M, Kiyota T, Horiba M, Buescher JL, Walsh SM, Gendelman HE, Ikezu T. Interferon-gamma and tumor necrosis factor-alpha regulate amyloid-beta plaque deposition and beta-secretase expression in Swedish mutant APP transgenic mice. Am J Pathol. 2007;170:680–92.PubMedPubMedCentralCrossRef
20.
Liao YF, Wang BJ, Cheng HT, Kuo LH, Wolfe MS. Tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway. J Biol Chem. 2004;279:49523–32.PubMedCrossRef
21.
Vom Berg J, Prokop S, Miller KR, Obst J, Kalin RE, Lopategui-Cabezas I, Wegner A, Mair F, Schipke CG, Peters O, et al. Inhibition of IL-12/IL-23 signaling reduces Alzheimer’s disease-like pathology and cognitive decline. Nat Med. 2012;18:1812–9.PubMedCrossRef
22.
23.
Neumeier M, Weigert J, Schaffler A, Weiss T, Kirchner S, Laberer S, Scholmerich J, Buechler C. Regulation of adiponectin receptor 1 in human hepatocytes by agonists of nuclear receptors. Biochem Biophys Res Commun. 2005;334:924–9.PubMedCrossRef
24.
Bonnard C, Durand A, Vidal H, Rieusset J. Changes in adiponectin, its receptors and AMPK activity in tissues of diet-induced diabetic mice. Diabetes Metab. 2008;34:52–61.PubMedCrossRef
25.
Walder K, Kerr-Bayles L, Civitarese A, Jowett J, Curran J, Elliott K, Trevaskis J, Bishara N, Zimmet P, Mandarino L, et al. The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes. Diabetologia. 2005;48:459–68.PubMedCrossRef
26.
Ding G, Qin Q, He N, Francis-David SC, Hou J, Liu J, Ricks E, Yang Q. Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor gamma. J Mol Cell Cardiol. 2007;43:73–84.PubMedPubMedCentralCrossRef
27.
Bluher M, Fasshauer M, Kralisch S, Schon MR, Krohn K, Paschke R. Regulation of adiponectin receptor R1 and R2 gene expression in adipocytes of C57BL/6 mice. Biochem Biophys Res Commun. 2005;329:1127–32.PubMedCrossRef
28.
Palanivel R, Fang X, Park M, Eguchi M, Pallan S, De Girolamo S, Liu Y, Wang Y, Xu A, Sweeney G. Globular and full-length forms of adiponectin mediate specific changes in glucose and fatty acid uptake and metabolism in cardiomyocytes. Cardiovasc Res. 2007;75:148–57.PubMedCrossRef
29.
Nishizawa H, Shimomura I, Kishida K, Maeda N, Kuriyama H, Nagaretani H, Matsuda M, Kondo H, Furuyama N, Kihara S, et al. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes. 2002;51:2734–41.PubMedCrossRef
30.
Kang KH, Higashino A, Kim HS, Lee YT, Kageyama T. Molecular cloning, gene expression, and tissue distribution of adiponectin and its receptors in the Japanese monkey, Macaca fuscata. J Med Primatol. 2009;38:77–85.PubMedCrossRef
31.
Shimada K, Miyazaki T, Daida H. Adiponectin and atherosclerotic disease. Clin Chim Acta. 2004;344:1–12.PubMedCrossRef
32.
Amira OC, Naicker S, Manga P, Sliwa K, Mia A, Raal F, Crowther NJ, Immelman RA, Olorunju S. Adiponectin and atherosclerosis risk factors in African hemodialysis patients: a population at low risk for atherosclerotic cardiovascular disease. Hemodial Int. 2012;16:59–68.PubMed
33.
Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K. Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol. 2003;14:561–6.PubMedCrossRef
34.
Wulster-Radcliffe MC, Ajuwon KM, Wang J, Christian JA, Spurlock ME. Adiponectin differentially regulates cytokines in porcine macrophages. Biochem Biophys Res Commun. 2004;316:924–9.PubMedCrossRef
35.
Otake H, Shite J, Shinke T, Watanabe S, Tanino Y, Ogasawara D, Sawada T, Hirata K, Yokoyama M. Relation between plasma adiponectin, high-sensitivity C-reactive protein, and coronary plaque components in patients with acute coronary syndrome. Am J Cardiol. 2008;101:1–7.PubMedCrossRef
36.
37.
Qi Y, Takahashi N, Hileman SM, Patel HR, Berg AH, Pajvani UB, Scherer PE, Ahima RS. Adiponectin acts in the brain to decrease body weight. Nat Med. 2004;10:524–9.PubMedCrossRef
38.
Yau SY, Li A, Hoo RL, Ching YP, Christie BR, Lee TM, Xu A, So KF. Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin. Proc Natl Acad Sci U S A. 2014;111:15810–5.PubMedPubMedCentralCrossRef
39.
Chabry J, Nicolas S, Cazareth J, Murris E, Guyon A, Glaichenhaus N, Heurteaux C, Petit-Paitel A. Enriched environment decreases microglia and brain macrophages inflammatory phenotypes through adiponectin-dependent mechanisms: relevance to depressive-like behavior. Brain Behav Immun. 2015;50:275–87.PubMedCrossRef
40.
Zhang D, Wang X, Wang B, Garza JC, Fang X, Wang J, Scherer PE, Brenner R, Zhang W, Lu XY. Adiponectin regulates contextual fear extinction and intrinsic excitability of dentate gyrus granule neurons through AdipoR2 receptors. Mol Psychiatry. 2017;22:1044–55.PubMedCrossRef
41.
Sun F, Lei Y, You J, Li C, Sun L, Garza J, Zhang D, Guo M, Scherer PE, Lodge D, Lu XY. Adiponectin modulates ventral tegmental area dopamine neuron activity and anxiety-related behavior through AdipoR1. Mol Psychiatry. 2018.
42.
Zhang K, Guo Y, Ge Z, Zhang Z, Da Y, Li W, Zhang Z, Xue Z, Li Y, Ren Y, et al. Adiponectin suppresses T helper 17 cell differentiation and limits autoimmune CNS inflammation via the SIRT1/PPARgamma/RORgammat pathway. Mol Neurobiol. 2017;54:4908–20.PubMedCrossRef
43.
Piccio L, Cantoni C, Henderson JG, Hawiger D, Ramsbottom M, Mikesell R, Ryu J, Hsieh CS, Cremasco V, Haynes W, et al. Lack of adiponectin leads to increased lymphocyte activation and increased disease severity in a mouse model of multiple sclerosis. Eur J Immunol. 2013;43:2089–100.PubMedPubMedCentralCrossRef
44.
Li X, Guo H, Zhao L, Wang B, Liu H, Yue L, Bai H, Jiang H, Gao L, Feng D, Qu Y. Adiponectin attenuates NADPH oxidase-mediated oxidative stress and neuronal damage induced by cerebral ischemia-reperfusion injury. Biochim Biophys Acta. 2017;1863:3265–76.CrossRef
45.
Miao J, Shen LH, Tang YH, Wang YT, Tao MX, Jin KL, Zhao YJ, Yang GY. Overexpression of adiponectin improves neurobehavioral outcomes after focal cerebral ischemia in aged mice. CNS Neurosci Ther. 2013;19:969–77.PubMedCrossRefPubMedCentral
46.
Nicolas S, Cazareth J, Zarif H, Guyon A, Heurteaux C, Chabry J, Petit-Paitel A. Globular adiponectin limits microglia pro-inflammatory phenotype through an AdipoR1/NF-kappaB signaling pathway. Front Cell Neurosci. 2017;11:352.PubMedPubMedCentralCrossRef
47.
Chan KH, Lam KS, Cheng OY, Kwan JS, Ho PW, Cheng KK, Chung SK, Ho JW, Guo VY, Xu A. Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity. PLoS One. 2012;7:e52354.PubMedPubMedCentralCrossRef
48.
Ng RC, Cheng OY, Jian M, Kwan JS, Ho PW, Cheng KK, Yeung PK, Zhou LL, Hoo RL, Chung SK, et al. Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice. Mol Neurodegener. 2016;11:71.PubMedPubMedCentralCrossRef
49.
Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, et al. Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci. 2006;26:10129–40.PubMedCrossRefPubMedCentral
50.
Fayad R, Pini M, Sennello JA, Cabay RJ, Chan L, Xu A, Fantuzzi G. Adiponectin deficiency protects mice from chemically induced colonic inflammation. Gastroenterology. 2007;132:601–14.PubMedCrossRef
51.
Yick LW, Ma OK, Ng RC, Kwan JS, Chan KH. Aquaporin-4 autoantibodies from neuromyelitis optica spectrum disorder patients induce complement-independent immunopathologies in mice. Front Immunol. 2018;9:1438.PubMedPubMedCentralCrossRef
52.
53.
Liu YJ, Chern Y. AMPK-mediated regulation of neuronal metabolism and function in brain diseases. J Neurogenet. 2015;29:50–8.PubMedCrossRef
54.
Heiker JT, Kosel D, Beck-Sickinger AG. Molecular mechanisms of signal transduction via adiponectin and adiponectin receptors. Biol Chem. 2010;391:1005–18.PubMedCrossRef
55.
Salminen A, Hyttinen JM, Kaarniranta K. AMP-activated protein kinase inhibits NF-kappaB signaling and inflammation: impact on healthspan and lifespan. J Mol Med (Berl). 2011;89:667–76.CrossRef
56.
von Bernhardi R, Eugenin-von Bernhardi L, Eugenin J. Microglial cell dysregulation in brain aging and neurodegeneration. Front Aging Neurosci. 2015;7:124.
57.
58.
Song J, Choi SM, Kim BC. Adiponectin regulates the polarization and function of microglia via PPAR-gamma signaling under amyloid beta toxicity. Front Cell Neurosci. 2017;11:64.PubMedPubMedCentral
59.
Wu L, Zhang L, Li B, Jiang H, Duan Y, Xie Z, Shuai L, Li J, Li J. AMP-activated protein kinase (AMPK) regulates energy metabolism through modulating thermogenesis in adipose tissue. Front Physiol. 2018;9:122.PubMedPubMedCentralCrossRef
60.
61.
Park H, Kam TI, Kim Y, Choi H, Gwon Y, Kim C, Koh JY, Jung YK. Neuropathogenic role of adenylate kinase-1 in Abeta-mediated tau phosphorylation via AMPK and GSK3beta. Hum Mol Genet. 2012;21:2725–37.PubMedCrossRef
62.
Dasgupta B, Seibel W. Compound C/dorsomorphin: its use and misuse as an AMPK inhibitor. Methods Mol Biol. 2018;1732:195–202.PubMedCrossRef
63.
Shah SA, Yoon GH, Chung SS, Abid MN, Kim TH, Lee HY, Kim MO. Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer’s disease neuropathological deficits. Mol Psychiatry. 2017;22:407–16.PubMedCrossRef
64.
Sag D, Carling D, Stout RD, Suttles J. Adenosine 5′-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype. J Immunol. 2008;181:8633–41.PubMedCrossRef
65.
Vallabhapurapu S, Karin M. Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol. 2009;27:693–733.PubMedCrossRef
66.
Wan F, Lenardo MJ. The nuclear signaling of NF-kappaB: current knowledge, new insights, and future perspectives. Cell Res. 2010;20:24–33.PubMedCrossRef
67.
Christian F, Smith EL, Carmody RJ. The regulation of NF-kappaB subunits by phosphorylation. Cells. 2016:5.
68.
Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A. Antagonistic crosstalk between NF-kappaB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal. 2013;25:1939–48.PubMedCrossRef
69.
Wang Y, Zhou Y, Graves DT. FOXO transcription factors: their clinical significance and regulation. Biomed Res Int. 2014;2014:925350.PubMedPubMedCentral
70.
Alvarez-Guardia D, Palomer X, Coll T, Davidson MM, Chan TO, Feldman AM, Laguna JC, Vazquez-Carrera M. The p65 subunit of NF-kappaB binds to PGC-1alpha, linking inflammation and metabolic disturbances in cardiac cells. Cardiovasc Res. 2010;87:449–58.PubMedCrossRef
71.
Srivastava RA, Pinkosky SL, Filippov S, Hanselman JC, Cramer CT, Newton RS. AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases. J Lipid Res. 2012;53:2490–514.PubMedPubMedCentralCrossRef
72.
Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423:762–9.PubMedCrossRef
73.
Bjursell M, Ahnmark A, Bohlooly YM, William-Olsson L, Rhedin M, Peng XR, Ploj K, Gerdin AK, Arnerup G, Elmgren A, et al. Opposing effects of adiponectin receptors 1 and 2 on energy metabolism. Diabetes. 2007;56:583–93.PubMedCrossRef
74.
Zhao L, Chen S, Sherchan P, Ding Y, Zhao W, Guo Z, Yu J, Tang J, Zhang JH. Recombinant CTRP9 administration attenuates neuroinflammation via activating adiponectin receptor 1 after intracerebral hemorrhage in mice. J Neuroinflammation. 2018;15:215.PubMedPubMedCentralCrossRef
75.
76.
De Meyts P. The insulin receptor: a prototype for dimeric, allosteric membrane receptors? Trends Biochem Sci. 2008;33:376–84.PubMedCrossRef
77.
Kosel D, Heiker JT, Juhl C, Wottawah CM, Bluher M, Morl K, Beck-Sickinger AG. Dimerization of adiponectin receptor 1 is inhibited by adiponectin. J Cell Sci. 2010;123:1320–8.PubMedCrossRef
78.
Almabouada F, Diaz-Ruiz A, Rabanal-Ruiz Y, Peinado JR, Vazquez-Martinez R, Malagon MM. Adiponectin receptors form homomers and heteromers exhibiting distinct ligand binding and intracellular signaling properties. J Biol Chem. 2013;288:3112–25.PubMedCrossRef
79.
Wang Q, Wu J, Rowan MJ, Anwyl R. Beta-amyloid inhibition of long-term potentiation is mediated via tumor necrosis factor. Eur J Neurosci. 2005;22:2827–32.PubMedCrossRef
80.
Bhaskar K, Maphis N, Xu G, Varvel NH, Kokiko-Cochran ON, Weick JP, Staugaitis SM, Cardona A, Ransohoff RM, Herrup K, Lamb BT. Microglial derived tumor necrosis factor-alpha drives Alzheimer’s disease-related neuronal cell cycle events. Neurobiol Dis. 2014;62:273–85.PubMedCrossRef
81.
Lourenco MV, Clarke JR, Frozza RL, Bomfim TR, Forny-Germano L, Batista AF, Sathler LB, Brito-Moreira J, Amaral OB, Silva CA, et al. TNF-alpha mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer’s beta-amyloid oligomers in mice and monkeys. Cell Metab. 2013;18:831–43.PubMedCrossRef
82.
He P, Zhong Z, Lindholm K, Berning L, Lee W, Lemere C, Staufenbiel M, Li R, Shen Y. Deletion of tumor necrosis factor death receptor inhibits amyloid beta generation and prevents learning and memory deficits in Alzheimer’s mice. J Cell Biol. 2007;178:829–41.PubMedPubMedCentralCrossRef
83.
Tobinick E, Gross H, Weinberger A, Cohen H. TNF-alpha modulation for treatment of Alzheimer’s disease: a 6-month pilot study. MedGenMed. 2006;8:25.PubMedPubMedCentral
84.
Dursun E, Gezen-Ak D, Hanagasi H, Bilgic B, Lohmann E, Ertan S, Atasoy IL, Alaylioglu M, Araz OS, Onal B, et al. The interleukin 1 alpha, interleukin 1 beta, interleukin 6 and alpha-2-macroglobulin serum levels in patients with early or late onset Alzheimer’s disease, mild cognitive impairment or Parkinson’s disease. J Neuroimmunol. 2015;283:50–7.PubMedCrossRef
85.
Li Y, Liu L, Barger SW, Griffin WS. Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway. J Neurosci. 2003;23:1605–11.PubMedPubMedCentralCrossRef
86.
Boza-Serrano A, Yang Y, Paulus A, Deierborg T. Innate immune alterations are elicited in microglial cells before plaque deposition in the Alzheimer’s disease mouse model 5xFAD. Sci Rep. 2018;8:1550.PubMedPubMedCentralCrossRef
87.
Yin Z, Raj D, Saiepour N, Van Dam D, Brouwer N, Holtman IR, Eggen BJL, Moller T, Tamm JA, Abdourahman A, et al. Immune hyperreactivity of Abeta plaque-associated microglia in Alzheimer’s disease. Neurobiol Aging. 2017;55:115–22.PubMedCrossRef
88.
Tsai SJ. Effects of interleukin-1beta polymorphisms on brain function and behavior in healthy and psychiatric disease conditions. Cytokine Growth Factor Rev. 2017;37:89–97.PubMedCrossRef
89.
Giulian D, Baker TJ, Shih LC, Lachman LB. Interleukin 1 of the central nervous system is produced by ameboid microglia. J Exp Med. 1986;164:594–604.PubMedCrossRef
90.
91.
Pan W, Kastin AJ. TNFalpha transport across the blood-brain barrier is abolished in receptor knockout mice. Exp Neurol. 2002;174:193–200.PubMedCrossRef
92.
Mietelska-Porowska A, Wojda U. T Lymphocytes and inflammatory mediators in the interplay between brain and blood in Alzheimer’s disease: potential pools of new biomarkers. J Immunol Res. 2017;2017:4626540.PubMedPubMedCentralCrossRef
93.
Prinz M, Priller J. The role of peripheral immune cells in the CNS in steady state and disease. Nat Neurosci. 2017;20:136–44.PubMedCrossRef
94.
Spranger J, Verma S, Gohring I, Bobbert T, Seifert J, Sindler AL, Pfeiffer A, Hileman SM, Tschop M, Banks WA. Adiponectin does not cross the blood-brain barrier but modifies cytokine expression of brain endothelial cells. Diabetes. 2006;55:141–7.PubMedCrossRef
95.
Song J, Choi SM, Whitcomb DJ, Kim BC. Adiponectin controls the apoptosis and the expression of tight junction proteins in brain endothelial cells through AdipoR1 under beta amyloid toxicity. Cell Death Dis. 2017;8:e3102.PubMedPubMedCentralCrossRef
96.
Brendel M, Kleinberger G, Probst F, Jaworska A, Overhoff F, Blume T, Albert NL, Carlsen J, Lindner S, Gildehaus FJ, et al. Increase of TREM2 during aging of an Alzheimer’s disease mouse model is paralleled by microglial activation and amyloidosis. Front Aging Neurosci. 2017;9:8.PubMedPubMedCentralCrossRef
97.
Hamelin L, Lagarde J, Dorothee G, Leroy C, Labit M, Comley RA, de Souza LC, Corne H, Dauphinot L, Bertoux M, et al. Early and protective microglial activation in Alzheimer’s disease: a prospective study using 18F-DPA-714 PET imaging. Brain. 2016;139:1252–64.PubMedCrossRef
98.
99.
Condello C, Yuan P, Schain A, Grutzendler J. Microglia constitute a barrier that prevents neurotoxic protofibrillar Abeta42 hotspots around plaques. Nat Commun. 2015;6:6176.PubMedCrossRef
100.
101.
Prokop S, Miller KR, Heppner FL. Microglia actions in Alzheimer’s disease. Acta Neuropathol. 2013;126:461–77.PubMedCrossRef
102.
Liu J, Guo M, Zhang D, Cheng SY, Liu M, Ding J, Scherer PE, Liu F, Lu XY. Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity. Proc Natl Acad Sci U S A. 2012;109:12248–53.PubMedPubMedCentralCrossRef
103.
Horvath RJ, Nutile-McMenemy N, Alkaitis MS, Deleo JA. Differential migration, LPS-induced cytokine, chemokine, and NO expression in immortalized BV-2 and HAPI cell lines and primary microglial cultures. J Neurochem. 2008;107:557–69.PubMedPubMedCentralCrossRef
104.
Gosselin D, Skola D, Coufal NG, Holtman IR, Schlachetzki JCM, Sajti E, Jaeger BN, O’Connor C, Fitzpatrick C, Pasillas MP, et al. An environment-dependent transcriptional network specifies human microglia identity. Science. 2017;356.PubMedPubMedCentralCrossRef
Metadata
Title
Adiponectin suppresses amyloid-β oligomer (AβO)-induced inflammatory response of microglia via AdipoR1-AMPK-NF-κB signaling pathway
Authors
Min Jian
Jason Shing-Cheong Kwan
Myriam Bunting
Roy Chun-Laam Ng
Koon Ho Chan
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-019-1492-6

Other articles of this Issue 1/2019

Journal of Neuroinflammation 1/2019 Go to the issue

Research

Transplantation of neural precursors generated from spinal progenitor cells reduces inflammation in spinal cord injury via NF-κB pathway inhibition

Research

A novel small molecular NLRP3 inflammasome inhibitor alleviates neuroinflammatory response following traumatic brain injury

Research

Responses of perivascular macrophages to circulating lipopolysaccharides in the subfornical organ with special reference to endotoxin tolerance

Research

Role of NADPH oxidase-2 in the progression of the inflammatory response secondary to striatum excitotoxic damage

Research

AMPK activation attenuates inflammatory pain through inhibiting NF-κB activation and IL-1β expression

Research

CD55 upregulation in astrocytes by statins as potential therapy for AQP4-IgG seropositive neuromyelitis optica