Acute and subacute IL-1β administrations differentially modulate neuroimmune and neurotrophic systems: possible implications for neuroprotection and neurodegeneration

Journal of Neuroinflammation

Yilong Dong¹  Ye Zhang²  Cai Song³ 

[1] School of Life Science, No.2 Cuihu Bei Road, Kunming, Yunnan, 650091, China;Research Institute of Marine Drug and Nutrition, Guangdong Ocean University, Zhanjiang, Guangdong, China;Department of Biomedical Science, University of Prince Edward Island, 550 University Ave, Charlottetown, C1A 4P3, Canada

关键词: Cytokines;    Neurotrophin receptors;    Neurotrophins;    Memory;    Astrocytes;    Microglia;    Acute and 8 day repeated IL-1β administration;   

Others  :  1159979
DOI  :  10.1186/1742-2094-10-59

 received in 2013-02-28, accepted in 2013-04-22,  发布年份 2013

【 摘 要 】

Background

In Alzheimer’s disease, stroke and brain injuries, activated microglia can release proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines may change astrocyte and neurotrophin functions, which influences neuronal survival and induces apoptosis. However, the interaction between neuroinflammation and neurotrophin functions in different brain conditions is unknown. The present study hypothesized that acute and subacute elevated IL-1β differentially modulates glial and neurotrophin functions, which are related to their role in neuroprotection and neurodegeneration.

Method

Rats were i.c.v. injected with saline or IL-1β for 1 or 8 days and tested in a radial maze. mRNA and protein expressions of glial cell markers, neurotrophins, neurotrophin receptors, β-amyloid precursor protein (APP) and the concentrations of pro- and anti-inflammatory cytokines were measured in the hippocampus.

Results

When compared to controls, memory deficits were found 4 days after IL-1 administrations, however the deficits were attenuated by IL-1 receptor antagonist (RA). Subacute IL-1 administrations increased expressions of APP, microglial active marker CD11b, and p75 neurotrophin receptor, and the concentration of tumor necrosis factor (TNF)-α and IL-1β, but decreased expressions of astrocyte active marker glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and TrK B. By contrast, up-regulations of NGF, BDNF and TrK B expressions were found after acute IL-1 administration, which are associated with the increase in both glial marker expressions and IL-10 concentrations. However, TrK A was down-regulated by acute and up-regulated by subacute IL-1 administrations. Subacute IL-1-induced changes in the glial activities, cytokine concentrations and expressions of BDNF and p75 were reversed by IL-1RA treatment.

Conclusion

These results indicate that acute and subacute IL-1 administrations induce different changes toward neuroprotection after acute IL-1 administrations but neurodegeneration after subacute ones.

【 授权许可】

   
2013 Song et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Block ML, Hong JS: Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 2005, 76:77-98.
• [2]Sugama S, Takenouchi T, Cho BP, Joh TH, Hashimoto M, Kitani H: Possible roles of microglial cells for neurotoxicity in clinical neurodegenerative diseases and experimental animal models. Inflamm Allergy Drug Targets 2009, 8:277-284.
• [3]Griffin WS, Mrak RE: Interleukin-1 in the genesis and progression of and risk for development of neuronal degeneration in Alzheimer's disease. J Leukoc Biol 2002, 72:233-238.
• [4]Griffin WS, Liu L, Li Y, Mrak RE, Barger SW: Interleukin-1 mediates Alzheimer and Lewy body pathologies. J Neuroinflam 2006, 3:5. BioMed Central Full Text
• [5]Taepavarapruk P, Song C: Reductions of acetylcholine release and nerve growth factor expression are correlated with memory impairment induced by interleukin-1beta administrations: effects of omega-3 fatty acid EPA treatment. J Neurochem 2010, 112:1054-1064.
• [6]Song C: The effect of thymectomy and IL-1 on memory: implications for the relationship between immunity and depression. Brain Behav Immun 2002, 16:557-568.
• [7]Patel HC, Ross FM, Heenan LE, Davies RE, Rothwell NJ, Allan SM: Neurodegenerative actions of interleukin-1 in the rat brain are mediated through increases in seizure activity. J Neurosci Res 2006, 83:385-391.
• [8]Shin JA, Park EM, Choi JS, Seo SM, Kang JL, Lee KE, Cho S: Ischemic preconditioning-induced neuroprotection is associated with differential expression of IL-1beta and IL-1 receptor antagonist in the ischemic cortex. J Neuroimmunol 2009, 217:14-19.
• [9]Tuttolomondo A, Di Raimondo D, di Sciacca R, Pinto A, Licata G: Inflammatory cytokines in acute ischemic stroke. Curr Pharm Des 2008, 14:3574-3589.
• [10]Petcu EB, Kocher T, Kuhr A, Buga AM, Klöting I, Herndon JG, Kessler C, Popa-Wagner A: Mild systemic inflammation has a neuroprotective effect after stroke in rats. Curr Neurovasc Res 2008, 5:214-223.
• [11]Pickering M, O'Connor JJ: Pro-inflammatory cytokines and their effects in the dentate gyrus. Prog Brain Res 2007, 163:339-354.
• [12]Marschinke F, Strömberg I: Dual effects of TNFalpha on nerve fiber formation from ventral mesencephalic organotypic tissue cultures. Brain Res 2008, 1215:30-39.
• [13]Brough D, Tyrrell PJ, Allan SM: Regulation of interleukin-1 in acute brain injury. Trends Pharmacol Sci 2011, 32:617-622.
• [14]Matarredona ER, Santiago M, Venero JL, Cano J, Machado A: Group II metabotropic glutamate receptor activation protects striatal dopaminergic nerve terminals against MPP+-induced neurotoxicity along with brain-derived NTF induction. J Neurochem 2001, 76:351-360.
• [15]Cadete-Leite A, Pereira PA, Madeira MD, Paula-Barbosa MM: Nerve growth factor prevents cell death and induces hypertrophy of basal forebrain cholinergic neurons in rats withdrawn from prolonged ethanol intake. Neuroscience 2003, 119:1055-1069.
• [16]Swanson RA, Ying W, Kauppinen TM: Astrocyte influences on ischemic neuronal death. Curr Mol Med 2004, 4:193-205.
• [17]Kerschensteiner M, Meinl E, Hohlfeld R: Neuro-immune crosstalk in CNS diseases. Neuroscience 2009, 158:1122-1132.
• [18]Dawbarn D, Allen SJ: Neurotrophins and neurodegeneration. Neuropathol Appl Neurobiol 2003, 29:211-230.
• [19]Bibel M, Barde YA: Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev 2000, 14:2919-2937.
• [20]Bredesen DE, Mehlen P, Rabizadeh S: Apoptosis and dependence receptors: a molecular basis for cellular addiction. Physiol Rev 2004, 84:411-430.
• [21]Leibinger M, Müller A, Andreadaki A, Hauk TG, Kirsch M, Fischer D: Neuroprotective and axon growth-promoting effects following inflammatory stimulation on mature retinal ganglion cells in mice depend on ciliary neurotrophic factor and leukemia inhibitory factor. J Neurosci 2009, 29:14334-14341.
• [22]Wu MD, Hein AM, Moravan MJ, Shaftel SS, Olschowka JA, O'Banion MK, Winter CD, Iannotti F, Pringle AK, Trikkas C, Clough GF, Church MK: A microdialysis method for the recovery of IL-1beta, IL-6 and nerve growth factor from human brain in vivo. J Neurosci Methods 2002, 119:45-50.
• [23]Mattson MP, Barger SW, Furukawa K, Bruce AJ, Wyss-Coray T, Mark RJ, Mucke L: Cellular signaling roles of TGF beta, TNF alpha and beta APP in brain injury responses and Alzheimer's disease. Brain Res Brain Res Rev 1997, 23:47-61.
• [24]Ikeda O, Murakami M, Ino H, Yamazaki M, Nemoto T, Koda M, Nakayama C, Moriya H: Acute up-regulation of brain-derived neurotrophic factor expression resulting from experimentally induced injury in the rat spinal cord. Acta Neuropathol 2001, 102:239-245.
• [25]Hayashida K, Clayton BA, Johnson JE, Eisenach JC: Brain derived nerve growth factor induces spinal noradrenergic fiber sprouting and enhances clonidine analgesia following nerve injury in rats. Pain 2008, 136:348-355.
• [26]Hock C, Heese K, Hulette C, Rosenberg C, Otten U: Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch Neurol 2000, 57:846-851.
• [27]Rojo LE, Fernández JA, Maccioni AA, Jimenez JM, Maccioni RB: Neuroinflammation: implications for the pathogenesis and molecular diagnosis of Alzheimer's disease. Arch Med Res 2008, 39:1-16.
• [28]Song C, Phillips AG, Leonard BE, Horrobin DF: Ethyl-eicosapentaenoic acid ingestion prevents corticosterone-mediated memory impairment induced by central administration of interleukin-1beta in rats. Mol Psychiatry 2004, 9:630-638.
• [29]Song C, Horrobin DF: Omega-3 fatty acid ethyl-eicosapentaenoic acid but not soybean oil attenuates memory impairment induced by central IL-1beta-administration. J Lipid Res 2004, 45:1112-1121.
• [30]Song C, Leonard BE: The comparison of changes in behavior, neurochemistry, endocrine, and immune functions after different routes, doses and durations of administrations of IL-1beta in rats. Pharmacopsychiatry 2006, 39:88-99.
• [31]Luchtman DW, Shao D, Song C: Behavior, neurotransmitters and inflammation in three regimens of the MPTP mouse model of Parkinson's disease. Physiol Behav 2009, 98:130-138.
• [32]Datta SC, Opp MR: Lipopolysaccharide-induced increases in cytokines in discrete mouse brain regions are detectable using Luminex xMAP((R)) technology. J Neurosci Methods 2008, 75:119-124.
• [33]Proescholdt MG, Chakravarty S, Foster JA, Foti SB, Briley EM, Herkenham M: Intracerebroventricular but not intravenous interleukin-1beta induces widespread vascular-mediated leukocyte infiltration and immune signal mRNA expression followed by brain-wide glial activation. Neuroscience 2002, 112:731-749.
• [34]Ghosh S, Wu MD, Shaftel SS, Kyrkanides S, Laferla FM, Olschowka JA, O'Banion MK: Sustained interleukin-1β overexpression exacerbates tau pathology despite reduced amyloid burden in an Alzheimer's mouse model. J Neurosci 2013, 33:5053-5064.
• [35]Siegel GJ, Chauhan NB: Neurotrophic factors in Alzheimer’s and Parkinson’s disease brain. Brain Res Brain Res Rev 2000, 33:199-227.
• [36]Villoslada P, Genain CP: Role of nerve growth factor and other trophic factors in brain inflammation. Prog Brain Res 2004, 146:403-414.
• [37]Heneka MT, Sastre M, Dumitrescu-Ozimek L, Hanke A, Dewachter I, Kuiperi C, O'Banion K, Klockgether T, Van Leuven F, Landreth GE: Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. Brain 2005, 128:1442-1453.
• [38]Browne KD, Iwata A, Putt ME, Smith DH: Chronic ibuprofen administration worsens cognitive outcome following traumatic brain injury in rats. Exp Neurol 2006, 201:301-307.
• [39]Sofroniew MV: Reactive astrocytes in neural repair and protection. Neuroscientist 2005, 11:400-407.
• [40]Smits HA, van Beelen AJ, de Vos NM, Rijsmus A, van der Bruggen T, Verhoef J, van Muiswinkel FL, Nottet HS: Activation of human macrophages by amyloid-beta is attenuated by astrocytes. J Immunol 2001, 166:6869-6876.
• [41]Saragovi HU, Hamel E, Di Polo A: A neurotrophic rationale for the therapy of neurodegenerative disorders. Curr Alzheimer Res 2009, 6:419-423.
• [42]Carlson NG, Wieggel WA, Chen J, Bacchi A, Rogers SW, Gahring LC: Inflammatory cytokines IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha impart neuroprotection to an excitotoxin through distinct pathways. J Immunol 1999, 163:3963-3968.
• [43]Arancio O, Chao MV: Neurotrophins, synaptic plasticity and dementia. Curr Opin Neurobiol 2007, 17:325-330.
• [44]Bossers K, Meerhoff G, Balesar R, van Dongen JW, Kruse CG, Swaab DF, Verhaagen J: Analysis of gene expression in Parkinson’s disease: possible involvement of neurotrophic support and axon guidance in dopaminergic cell death. Brain Pathol 2009, 19:91-107.
• [45]Schulte-Herbrüggen O, Jockers-Scherübl MC, Hellweg R: Neurotrophins: from pathophysiology to treatment in Alzheimer's disease. Curr Alzheimer Res 2008, 5:38-44.
• [46]Evans JR, Barker RA: Neurotrophic factors as a therapeutic target for Parkinson's disease. Expert Opin Ther Targets 2008, 12:437-447.
• [47]Wu MD, Hein AM, Moravan MJ, Shaftel SS, Olschowka JA, O'Banion MK: Adult murine hippocampal neurogenesis is inhibited by sustained IL-1β and not rescued by voluntary running. Brain Behav Immun 2012, 26:292-300.
• [48]Peng S, Wuu J, Mufson EJ, Fahnestock M: Precursor form of brain-derived NTF and mature brain-derived NTF are decreased in the pre-clinical stages of Alzheimer's disease. J Neurochem 2005, 93:1412-1421.
• [49]Peng S, Garzon DJ, Marchese M, Klein W, Ginsberg SD, Francis BM, Mount HT, Mufson EJ, Salehi A, Fahnestock M: Decreased brain-derived neurotrophic factor depends on amyloid aggregation state in transgenic mouse models of Alzheimer's disease. J Neurosci 2009, 29:9321-9329.
• [50]Li G, Peskind ER, Millard SP, Chi P, Sokal I, Yu CE, Bekris LM, Raskind MA, Galasko DR, Montine TJ: Cerebrospinal fluid concentration of brain-derived neurotrophic factor and cognitive function in non-demented subjects. PLoS One 2009, 4:5424.
• [51]Gobbo OL, O'Mara SM: Exercise, but not environmental enrichment, improves learning after kainic acid-induced hippocampal neurodegeneration in association with an increase in brain-derived NTF. Behav Brain Res 2005, 159:21-26.
• [52]Volosin M, Song W, Almeida RD, Kaplan DR, Hempstead BL, Friedman WJ: Interaction of survival and death signaling in basal forebrain neurons: roles of neurotrophins and proneurotrophins. J Neurosci 2006, 26:7756-7766.
• [53]Ginsberg SD, Che S, Wuu J, Counts SE, Mufson EJ: Down regulation of trk but not p75NTR gene expression in single cholinergic basal forebrain neurons mark the progression of Alzheimer's disease. J Neurochem 2006, 97:475-487.
• [54]D'Onofrio M, Arisi I, Brandi R, Di Mambro A, Felsani A, Capsoni S, Cattaneo A: Early inflammation and immune response mRNAs in the brain of AD11 anti-NGF mice. Neurobiol Aging 2011, 32:1007-1022.
• [55]Rohe M, Synowitz M, Glass R, Paul SM, Nykjaer A, Willnow TE: Brain-derived neurotrophic factor reduces amyloidogenic processing through control of SORLA gene expression. J Neurosci 2009, 29:15472-15478.
• [56]Coulson EJ: Does p75 neurotrophin receptor mediate Aβ-induced toxicity in Alzheimer’s disease? J Neurochem 2006, 98:654-660.
• [57]Chakravarthy B, Gaudet C, Ménard M, Atkinson T, Brown L, Laferla FM, Armato U, Whitfield J: Amyloid-beta peptides stimulate the expression of the p75NTR neurotrophin receptor in SHSY5Y human neuroblastoma cells and AD transgenic mice. J Alzheimer’s Dis 2010, 19:915-925.
• [58]Hein AM, Stasko MR, Matousek SB, Scott-McKean JJ, Maier SF, Olschowka JA, Costa AC, O'Banion MK: Sustained hippocampal IL-1beta overexpression impairs contextual and spatial memory in transgenic mice. Brain Behav Immun 2010, 24:243-253.
• [59]Knipper M, da Penha BM, Blöchl A, Breer H, Thoenen H, Lindholm D: Positive feedback between acetylcholine and the neurotrophins nerve growth factor and brain-derived neurotrophic factor in the rat hippocampus. Eur J Neurosci 1994, 6:668-671.
• [60]Auld DS, Mennicken F, Day JC, Quirion R: Neurotrophins differentially enhance acetylcholine release, acetylcholine content and choline acetyltransferase activity in basal forebrain neurons. J Neurochem 2001, 77:253-262.
• [61]Song C, Phillips AG, Leonard B: Interleukin 1 beta enhances conditioned fear memory in rats: possible involvement of glucocorticoids. Eur J Neurosci 2003, 18:1739-1743.
• [62]Yirmiya R, Winocur G, Goshen I: Brain interleukin-1 is involved in spatial memory and passive avoidance conditioning. Neurobiol Learn Mem 2002, 78:379-389.
• [63]Coulson EJ, May LM, Sykes AM, Hamlin AS: The role of the p75 neurotrophin receptor in cholinergic dysfunction in Alzheimer's disease. Neuroscientist 2009, 15:317-323.
• [64]Barrientos RM, Sprunger DB, Campeau S, Watkins LR, Rudy JW, Maier SF: BDNF mRNA expression in rat hippocampus following contextual learning is blocked by intrahippocampal IL-1beta administration. J Neuroimmunol 2004, 2155:119-126.