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Acta Neuropathologica
Published in: Acta Neuropathologica 3/2010

01-09-2010 | Review

Contribution of systemic inflammation to chronic neurodegeneration

Author: V. Hugh Perry

Published in: Acta Neuropathologica | Issue 3/2010

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Abstract

Systemic infection or inflammation gives rise to signals that communicate with the brain and leads to changes in metabolism and behaviour collectively known as sickness behaviour. In healthy young individuals, these changes are normally transient with no long-term consequences. The microglia are involved in the immune to brain signalling pathways. In the aged or diseased brain, the microglia have a primed phenotype as a consequence of changes in their local microenvironment. Systemic inflammation impacts on these primed microglia and switches them from a relatively benign to an aggressive phenotype with the enhanced synthesis of pro-inflammatory mediators. Recent evidence suggests that systemic inflammation contributes to the exacerbation of acute symptoms of chronic neurodegenerative disease and may accelerate disease progression. The normal homeostatic role that microglia play in signalling about systemic infections and inflammation becomes maladaptive in the aged and diseased brain and this offers a route to therapeutic intervention. Prompt treatment of systemic inflammation or blockade of signalling pathways from the periphery to the brain may help to slow neurodegeneration and improve the quality of life for individuals suffering from chronic neurodegenerative disease.
Literature
1.
Aguzzi A, Sigurdson C, Heikenwaelder M (2008) Molecular mechanisms of prion pathogenesis. Annu Rev Pathol 3:11–40PubMed
2.
Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi M (2007) Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10:1538–1543PubMed
3.
Andersson PB, Perry VH, Gordon S (1992) The acute inflammatory response to lipopolysaccharide in CNS parenchyma differs from that in other body tissues. Neuroscience 48(1):169–186PubMed
4.
Barclay AN, Wright GJ, Brooke G, Brown MH (2002) CD200 and membrane protein interactions in the control of myeloid cells. Trends Immunol 23:285–290PubMed
5.
Barnham KJ, Cappai R, Beyreuther K, Masters CL, Hill AF (2006) Delineating common molecular mechanisms in Alzheimer’s and prion diseases. Trends Biochem Sci 31(8):465–472PubMed
6.
Barron RM, Campbell SL, King D et al (2007) High titers of transmissible spongiform encephalopathy infectivity associated with extremely low levels of PrPSc in vivo. J Biol Chem 282(49):35878–35886PubMed
7.
Beers DR, Henkel JS, Xiao Q et al (2006) Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 103(43):16021–16026PubMed
8.
Betmouni S, Perry VH, Gordon JL (1996) Evidence for an early inflammatory response in the central nervous system of mice with scrapie. Neuroscience 74(1):1–5PubMed
9.
Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer’s disease. Lancet 368:387–403PubMed
10.
Bluthe RM, Laye S, Michaud B, Combe C, Dantzer R, Parnet P (2000) Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice. Eur J Neurosci 12:4447–4456PubMed
11.
Bluthe RM, Michaud B, Poli V, Dantzer R (2000) Role of IL-6 in cytokine-induced sickness behavior: a study with IL-6 deficient mice. Physiol Behav 70:367–373PubMed
12.
Boche D, Cunningham C, Docagne F, Scott H, Perry VH (2006) TGFbeta1 regulates the inflammatory response during chronic neurodegeneration. Neurobiol Dis 22:638–650PubMed
13.
Boissonneault V, Filali M, Lessard M, Relton J, Wong G, Rivest S (2009) Powerful beneficial effects of macrophage colony-stimulating factor on beta-amyloid deposition and cognitive impairment in Alzheimer’s disease. Brain 132:1078–1092PubMed
14.
Bruce ME, McConnell I, Fraser H, Dickinson AG (1991) The disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis. J Gen Virol 72:595–603PubMed
15.
Bucks RS, Gidron Y, Harris P, Teeling J, Wesnes JA, Perry VH (2008) Selective effects of upper respiratory tract infection on cognition, mood and emotion processing: a prospective study. Brain Behav Immun 22:399–407PubMed
16.
Buljevac D, Flach HZ, Hop WC et al (2002) Prospective study on the relationship between infections and multiple sclerosis exacerbations. Brain 125:952–960PubMed
17.
Campbell SJ, Perry VH, Pitossi FJ et al (2005) Central nervous system injury triggers hepatic CC and CXC chemokine expression that is associated with leukocyte mobilization and recruitment to both the central nervous system and the liver. Am J Pathol 166(5):1487–1497PubMed
18.
Cechetto DF, Hachinski V, Whitehead SN (2008) Vascular risk factors and Alzheimer’s disease. Expert Rev Neurother 8:743–750PubMed
19.
Combrinck MI, Perry VH, Cunningham C (2002) Peripheral infection evokes exaggerated sickness behaviour in pre-clinical murine prion disease. Neuroscience 112:7–11PubMed
20.
Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517PubMed
21.
Cunningham C, Campion S, Lunnon K et al (2009) Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease. Biol Psychiatry 15:304–312
22.
Cunningham C, Campion S, Teeling J, Felton L, Perry VH (2007) The sickness behaviour and CNS inflammatory mediator profile induced by systemic challenge of mice with synthetic double-stranded RNA (poly I:C). Brain Behav Immun 21:490–502PubMed
23.
Cunningham C, Deacon R, Wells H (2003) Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease. Eur J Neurosci 17(10):2147–2155PubMed
24.
Cunningham C, Wilcockson DC, Boche D, Perry VH (2005) Comparison of inflammatory and acute-phase responses in the brain and peripheral organs of the ME7 model of prion disease. J Virol 79:5174–5184PubMed
25.
Cunningham C, Wilcockson DC, Campion S, Lunnon K, Perry VH (2005) Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration. J Neurosci 25:9275–9284PubMed
26.
D’Ambrosi N, Finocchi P, Apolloni S et al (2009) The proinflammatory action of microglial P2 receptors is enhanced in SOD1 models for amyotrophic lateral sclerosis. J Immunol 183(7):4648–4656PubMed
27.
Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9:46–56PubMed
28.
Davalos D, Grutzendler J, Yang G et al (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8:752–758PubMed
29.
DiCarlo G, Wilcock D, Henderson D, Gordon M, Morgan D (2001) Intrahippocampal LPS injections reduce Abeta load in APP + PS1 transgenic mice. Neurobiol Aging 22(6):1007–1012PubMed
30.
Dilger RN, Johnson RW (2008) Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system. J Leukoc Biol 84(4):932–939PubMed
31.
Ek M, Engblom D, Saha S, Blomqvist A, Jakobsson PJ, Ericsson-Dahlstrand A (2001) Inflammatory response: pathway across the blood-brain barrier. Nature 410:430–431PubMed
32.
Exton MS (1997) Infection-induced anorexia: active host defence strategy. Appetite 29(3):369–383PubMed
33.
Felton LM, Cunningham C, Rankine EL, Waters S, Boche D, Perry VH (2005) MCP-1 and murine prion disease: separation of early behavioural dysfunction from overt clinical disease. Neurobiol Dis 20(2):283–295PubMed
34.
Fick DM, Agostini JV, Inouye SK (2002) Delirium superimposed on dementia: a systematic review. J Am Geriatr Soc 50:723–1732
35.
Field R, Campion S, Warren C, Murray C, Cunningham C (2010) Systemic challenge with the TLR3 agonist poly I:C induces amplified IFNalpha/beta and IL-1beta responses in the diseased brain and exacerbates chronic neurodegeneration. Brain Behav Immun 24:996–1007PubMed
36.
Fong TG, Tulebaev SR, Inouye SK (2009) Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol 5:210–220PubMed
37.
Fong TG, Jones RN, Shi P et al (2009) Delirium accelerates cognitive decline in Alzheimer disease. Neurology 72:1570–1575PubMed
38.
Godoy MC, Tarelli R, Ferrari CC, Sarchi MI, Pitossi FJ (2008) Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson’s disease. Brain 131:1880–1894
39.
Gordon S, Taylor R (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5:953–964PubMed
40.
Grathwohl SA, Kalin RE, Bolmont T (2009) Formation and maintenance of Alzheimer’s disease beta-amyloid plaques in the absence of microglia. Nat Neurosci 12(11):1361–1363PubMed
41.
Gray BC, Siskova Z, Perry VH, O’Connor V (2009) Selective presynaptic degeneration in the synaptopathy associated with ME7-induced hippocampal pathology. Neurobiol Dis 35(1):63–74PubMed
42.
Guenther K, Deacon RM, Perry VH, Rawlins JN (2001) Early behavioural changes in scrapie-affected mice and the influence of dapsone. Eur J Neurosci 14(2):401–409PubMed
43.
Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:387–1394
44.
Harold D, Abraham R, Hollingworth P et al (2009) Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet 41:1088–1093PubMed
45.
Harrison NA, Brydon L, Walker C et al (2009) Neural origins of human sickness in interoceptive responses to inflammation. Biol Psychiatry 66:415–422PubMed
46.
Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD (2009) Inflammation causes mood changes through alterations in subgenual cingulated activity and mesolimbic connectivity. Biol Psychiatry 66:407–414PubMed
47.
Hart BL (1998) Biological basis of the behavior of sick animals. Neurosci Biobehav Rev 12(2):123–137
48.
Herber DL, Roth LM, Wilson D et al (2004) Time-dependent reduction in Abeta levels after intracranial LPS administration in APP transgenic mice. Exp Neurol 190(1):245–253PubMed
49.
Herrmann I, Kellert M, Schmidt H et al (2006) Streptococcus pneumoniae infection aggravates experimental autoimmune encephalomyelitis via Toll-like receptor 2. Infect Immun 74:4841–4848PubMed
50.
Hoek RM, Ruuls SR, Murphy CA et al (2000) Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 290:1768–1771PubMed
51.
Holmes C, Boche D, Wilkinson D et al (2008) Long-term effects of Abeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 372(9634):216–223PubMed
52.
Holmes C, Cunningham C, Zotova E et al (2009) Systemic inflammation and disease progression in Alzheimer disease. Neurology 73:768–774PubMed
53.
Hope T, Keene J, Fairburn CG, Jacoby R, McShane R (1999) Natural history of behavioural changes and psychiatric symptoms in Alzheimer’s disease: a longitudinal study. Br J Psychiatry 174:39–44PubMed
54.
Hwang D, Lee IY, Yoo H et al (2009) A systems approach to prion disease. Mol Syst Biol 5:252PubMed
55.
Jackson JC, Gordon SM, Hart RP, Hopkins RO, Ely EW (2004) The association between delirium and cognitive decline: a review of the empirical literature. Neuropsychol Rev 14(2):87–98PubMed
56.
Kamer AR, Craig RG, Pirraglia E et al (2009) TNF-alpha and antibodies to periodontal bacteria discriminate between Alzheimer’s disease patients and normal subjects. J Neuroimmunol 216:92–97PubMed
57.
Kamer AR, Dasanayake AP, Craig RG et al (2008) Alzheimer’s disease and peripheral infections: the possible contribution from periodontal infections, model and hypothesis. J Alzheimers Dis 13:437–449PubMed
58.
Kiesecker JM, Skelly DK, Beard KH, Preisser E (1999) Behavioral reduction of infection risk. Proc Natl Acad Sci USA 96:9165–9168PubMed
59.
Kluger MJ (1991) Fever: role of pyrogens and cryogens. Physiol Rev 71(1):93–127PubMed
60.
Kodl CT, Seaquist ER (2008) Cognitive dysfunction and diabetes mellitus. Endocr Rev 29:494–511PubMed
61.
Konsman JP, Parnet P, Dantzer R (2002) Cytokine-induced sickness behaviour: mechanisms and implications. Trends Neurosci 25:154–159PubMed
62.
Krabbe KS, Reichenberg A, Yirmiya R et al (2005) Low-dose endotoxemia and human neuropsychological functions. Brain Behav Immun 19:453–460PubMed
63.
Lacroix S, Feinstein D, Rivest S (1998) The bacterial endotoxin lipopolysaccharide has the ability to target the brain in upregulating its membrane CD14 receptor within specific cellular populations. Brain Pathol 8:625–640PubMed
64.
Lambert JC, Heath S, Even G et al (2009) Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat Genet 41:1094–1099PubMed
65.
Lasmezas CI, Deslys JP, Robain O et al (1997) Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein. Science 275:402–405PubMed
66.
Lee JW, Lee YK, Yuk DY et al (2008) Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. J Neuroinflammation 5:37PubMed
67.
Lemstra AW, Groen in’t Woud JC, Hoozemans JJ (2007) Microglia activation in sepsis: a case-control study. J Neuroinflammation 4:4PubMed
68.
Letiembre M, Hao W, Liu Y et al (2007) Innate immune receptor expression in normal brain aging. Neuroscience 146(1):248–254PubMed
69.
Luchsinger JA (2008) Adiposity, hyperinsulinemia, diabetes and Alzheimer’s disease: an epidemiological perspective. Eur J Pharmacol 585:119–129PubMed
70.
Martinez FO, Sica A, Mantovani A, Locati M (2008) Macrophage activation and polarization. Front Biosci 13:453–461PubMed
71.
McColl BW, Allan SM, Rothwell NJ (2009) Systemic infection, inflammation and acute ischemic stroke. Neuroscience 158(3):1049–1061PubMed
72.
Mildner A, Schmidt H, Nitsche M et al (2007) Microglia in the adult brain arise from Ly-6ChiCCR2 + monocytes only under defined host conditions. Nat Neurosci 10:1544–1553PubMed
73.
Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969PubMed
74.
Murray C, Sanderson DJ, Barkus C et al (2010) Systemic inflammation induces acute working memory deficits in the primed brain: relevance for delirium. Neurobiol Aging (epub ahead of print). PubMed PMID: 20471138
75.
Nguyen MD, D’Aigle T, Gowing G, Julien JP, Rivest S (2004) Exacerbation of motor neuron disease by chronic stimulation of innate immunity in a mouse model of amyotrophic lateral sclerosis. J Neurosci 24:1340–1349PubMed
76.
Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318PubMed
77.
O’Shea M, Maytham EG, Linehan JM, Brandner S, Collinge J, Lloyd SE (2008) Investigation of mcp1 as a quantitative trait gene for prion disease incubation time in mouse. Genetics 180(1):559–566PubMed
78.
Oaten M, Stevenson RJ, Case TI (2009) Disgust as a disease-avoidance mechanism. Psychol Bull 135:303–321PubMed
79.
Pavlov VA, Tracey KJ (2005) The cholinergic anti-inflammatory pathway. Brain Behav Immun 19:493–499PubMed
80.
Perry VH, Cunningham C, Boche D (2002) Atypical inflammation in the central nervous system in prion disease. Curr Opin Neurol 15(3):349–354PubMed
81.
Perry VH, Cunningham C, Holmes C (2007) Systemic infections and inflammation affect chronic neurodegeneration. Nat Rev Immunol 7:161–167PubMed
82.
Perry VH, Matyszak MK, Fearn S (1993) Altered antigen expression of microglia in the aged rodent CNS. Glia 7(1):60–67PubMed
83.
Pott Godoy MC, Ferrari CC, Pitossi FJ (2010) Nigral neurodegeneration triggered by striatal AdIL-1 administration can be exacerbated by systemic IL-1 expression. J Neuroimmunol 222(1–2):29–39PubMed
84.
Qiu C, De Ronchi D, Fratiglioni L (2007) The epidemiology of the dementias: an update. Curr Opin Psychiatry 20:380–385PubMed
85.
Rankine EL, Hughes PM, Botham MS, Perry VH, Felton LM (2006) Brain cytokine synthesis induced by an intraparenchymal injection of LPS is reduced in MCP-1-deficient mice prior to leucocyte recruitment. Eur J Neurosci 24(1):77–86PubMed
86.
Ransohoff RM (2007) Microgliosis: the questions shape the answers. Nat Neurosci 10:1507–1509PubMed
87.
Ransohoff RM, Perry VH (2009) Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 27:119–145PubMed
88.
Reichenberg A, Yirmiya R, Schuld A et al (2001) Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry 58:445–452PubMed
89.
Sasmono RT, Oceandy D, Pollard JW et al (2003) A macrophage colony-stimulating factor receptor-green fluorescent protein transgene is expressed throughout the mononuclear phagocyte system of the mouse. Blood 101(3):1155–1163PubMed
90.
Savill J, Dransfield I, Gregory C, Haslett C (2002) A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2:65–975
91.
Schenk D, Barbour R, Dunn W et al (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400(6740):173–177PubMed
92.
Schiffenbauer J, Johnson H, Butfiloski E, Wegrzyn L, Soos J (1993) Staphylococcal enterotoxins can reactivate experimental allergic encephalomyelitis. Proc Natl Acad Sci USA 90:8543–8546PubMed
93.
Schindler MK, Forbes ME, Robbins ME, Riddle DR (2008) Aging-dependent changes in the radiation response of the adult rat brain. Int J Radiat Oncol Biol Phys 70:826–834PubMed
94.
Schroder K, Sweet MJ, Hume DA (2006) Signal integration between IFNgamma and TLR signalling pathways in macrophages. Immunobiology 211:511–524PubMed
95.
Seminowicz DA, Mayberg HS, McIntosh AR et al (2004) Limbic-frontal circuitry in major depression: a path modelling metanalysis. Neuroimage 22:409–418PubMed
96.
Sheng JG, Mrak RE, Griffin WS (1998) Enlarged and phagocytic, but not primed, interleukin-1 alpha-immunoreactive microglia increase with age in normal human brain. Acta Neuropathol 95(3):229–234PubMed
97.
Sibley WA, Bamford CR, Clark K (1985) Clinical viral infections and multiple sclerosis. Lancet 1:1313–1315PubMed
98.
Simard AR, Soulet D, Gowing G, Julien JP, Rivest S (2006) Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 49:489–502PubMed
99.
Siskova Z, Page A, O’Connor V, Perry VH (2009) Degenerating synaptic boutons in prion disease: microglia activation without synaptic stripping. Am J Pathol 175(4):1610–1621PubMed
100.
Sly LM, Krzesicki RF, Brashler JR et al (2001) Endogenous brain cytokine mRNA and inflammatory responses to lipopolysaccharide are elevated in the Tg2576 transgenic mouse model of Alzheimer’s disease. Brain Res Bull 56(6):581–588PubMed
101.
Smith T, Hewson A, Kingsley C, Leonard J, Cuzner M (1997) Interleukin-12 induces relapse in experimental allergic encephalomyelitis in the Lewis rat. Am J Pathol 150:1909–1917PubMed
102.
Stout RD, Jiang C, Matta B, Tietzel I, Watkins SK, Suttles J (2005) Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences. J Immunol 175:342–349PubMed
103.
Stout RD, Watkins SK, Suttles J (2009) Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages. J Leukoc Biol 86:1105–1109PubMed
104.
Teeling JL, Cunningham C, Newman TA, Perry VH (2010) The effect of non-steroidal anti-inflammatory agents on behavioural changes and cytokine production following systemic inflammation: Implications for a role of COX-1. Brain Behav Immun 24:409–419PubMed
105.
Teeling JL, Felton LM, Deacon RM, Cunningham C, Rawlins JN, Perry VH (2007) Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines. Brain Behav Immun 21:836–850PubMed
106.
van Gool WA, van de Beek D, Eikelenboom P (2010) Systemic infection and delirium: when cytokines and acetylcholine collide. Lancet 375:773–775PubMed
107.
Walker DG, Dalsing-Hernandez JE, Campbell NA, Lue LF (2009) Decreased expression of CD200 and CD200 receptor in Alzheimer’s disease: a potential mechanism leading to chronic inflammation. Exp Neurol 215:5–19PubMed
108.
Wirths O, Breyhan H, Marcello A, Cotel MC, Bruck W, Bayer TA (2010) Inflammatory changes are tightly associated with neurodegeneration in the brain and spinal cord of the APP/PS1KI mouse model of Alzheimer’s disease. Neurobiol Aging 31(5):747–757PubMed
109.
Yong VW, Rivest S (2009) Taking advantage of the systemic immune system to cure brain diseases. Neuron 64(1):55–60PubMed
110.
Zotova E, Nicoll JA, Kalaria R, Holmes C, Boche D (2010) Inflammation in Alzheimer’s disease: relevance to pathogenesis and therapy. Alzheimers Res Ther 2:1–9PubMed
Metadata
Title
Contribution of systemic inflammation to chronic neurodegeneration
Author
V. Hugh Perry
Publication date
01-09-2010
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 3/2010
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-010-0722-x

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