Insulin-like growth factor-I peptides act centrally to decrease depression-like behavior of mice treated intraperitoneally with lipopolysaccharide

Journal of Neuroinflammation

Robert H McCusker²  Keith W Kelley²  Robert Dantzer²  Marcus Lawson¹  Sook-Eun Park² 

[1] Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801-3873, USA;Department of Pathology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801-3873, USA

关键词: lipopolysaccharide;    sickness;    depression-like behavior;    IGF-I;   

Others  :  1212938
DOI  :  10.1186/1742-2094-8-179

 received in 2011-08-25, accepted in 2011-12-21,  发布年份 2011

【 摘 要 】

Centrally administered insulin-like growth factor (IGF)-I has anti-depressant activity in several rodent models, including lipopolysaccharide (LPS)-induced depression. In this study we tested the ability of IGF-I and GPE (the N-terminal tri-peptide derived from IGF-I) to alter depression-like behavior induced by intraperitoneal (i.p.) administration of LPS in a preventive and curative manner. In the first case, IGF-I (1 μg) or GPE (5 μg) was administered i.c.v. to CD-1 mice followed 30 min later by 330 μg/kg body weight i.p. LPS. In the second case, 830 μg/kg body weight LPS was given 24 h prior to either IGF-I or GPE. When administered i.p., LPS induced full-blown sickness assessed as a loss of body weight, decrease in food intake and sickness behavior. None of these indices were affected by IGF-I or GPE. LPS also induced depression-like behavior; assessed as an increased duration of immobility in the tail suspension and forced swim tests. When administered before or after LPS, IGF-I and GPE abrogated the LPS response; attenuating induction of depression-like behaviors and blocking preexistent depression-like behaviors. Similar to previous work with IGF-I, GPE decreased brain expression of cytokines in response to LPS although unlike IGF-I, GPE did not induce the expression of brain-derived neurotrophic factor (BDNF). LPS induced expression of tryptophan dioxygenases, IDO1, IDO2 and TDO2, but expression of these enzymes was not altered by GPE. Thus, both IGF-I and GPE elicit specific improvement in depression-like behavior independent of sickness, an action that could be due to their anti-inflammatory properties.

【 授权许可】

   
2011 Park et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Raison CL, Capuron L, Miller AH: Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006, 27:24-31.
• [2]Miller AH, Maletic V, Raison CL: Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 2009, 65:732-741.
• [3]Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW: From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008, 9:46-56.
• [4]Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A, Pollmacher T: Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry 2001, 58:445-452.
• [5]Eisenberger NI, Berkman ET, Inagaki TK, Rameson LT, Mashal NM, Irwin MR: Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward. Biol Psychiatry 2010, 68:748-754.
• [6]Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD: Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry 2009, 66:407-414.
• [7]Capuron L, Dantzer R: Cytokines and depression: the need for a new paradigm. Brain Behav Immun 2003, 17(Suppl 1):S119-124.
• [8]Capuron L, Gumnick JF, Musselman DL, Lawson DH, Reemsnyder A, Nemeroff CB, Miller AH: Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology 2002, 26:643-652.
• [9]Yirmiya R: Endotoxin produces a depressive-like episode in rats. Brain Res 1996, 711:163-174.
• [10]Frenois F, Moreau M, O'Connor J, Lawson M, Micon C, Lestage J, Kelley KW, Dantzer R, Castanon N: Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior. Psychoneuroendocrinology 2007, 32:516-531.
• [11]Park SE, Dantzer R, Kelley KW, McCusker RH: Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice. J Neuroinflammation 2011, 8:12. BioMed Central Full Text
• [12]Yirmiya R, Pollak Y, Barak O, Avitsur R, Ovadia H, Bette M, Weihe E, Weidenfeld J: Effects of antidepressant drugs on the behavioral and physiological responses to lipopolysaccharide (LPS) in rodents. Neuropsychopharmacology 2001, 24:531-544.
• [13]O'Connor JC, Lawson MA, Andre C, Moreau M, Lestage J, Castanon N, Kelley KW, Dantzer R: Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiatry 2009, 14:511-522.
• [14]Henry CJ, Huang Y, Wynne A, Hanke M, Himler J, Bailey MT, Sheridan JF, Godbout JP: Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia. J Neuroinflammation 2008, 5:15. BioMed Central Full Text
• [15]Gibb J, Hayley S, Poulter MO, Anisman H: Effects of stressors and immune activating agents on peripheral and central cytokines in mouse strains that differ in stressor responsivity. Brain Behav Immun 2011, 25:468-482.
• [16]Bay-Richter C, Janelidze S, Hallberg L, Brundin L: Changes in behaviour and cytokine expression upon a peripheral immune challenge. Behav Brain Res 2011, 222:193-199.
• [17]Damasio AR, Grabowski TJ, Bechara A, Damasio H, Ponto LL, Parvizi J, Hichwa RD: Subcortical and cortical brain activity during the feeling of self-generated emotions. Nat Neurosci 2000, 3:1049-1056.
• [18]Blood AJ, Zatorre RJ: Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proc Natl Acad Sci USA 2001, 98:11818-11823.
• [19]Kringelbach ML, O'Doherty J, Rolls ET, Andrews C: Activation of the human orbitofrontal cortex to a liquid food stimulus is correlated with its subjective pleasantness. Cereb Cortex 2003, 13:1064-1071.
• [20]Nitschke JB, Heller W, Etienne MA, Miller GA: Prefrontal cortex activity differentiates processes affecting memory in depression. Biol Psychol 2004, 67:125-143.
• [21]Burgdorf J, Wood PL, Kroes RA, Moskal JR, Panksepp J: Neurobiology of 50-kHz ultrasonic vocalizations in rats: electrode mapping, lesion, and pharmacology studies. Behav Brain Res 2007, 182:274-283.
• [22]Panksepp J, Normansell L, Cox JF, Siviy SM: Effects of neonatal decortication on the social play of juvenile rats. Physiol Behav 1994, 56:429-443.
• [23]Hodes GE, Hill-Smith TE, Lucki I: Fluoxetine treatment induces dose dependent alterations in depression associated behavior and neural plasticity in female mice. Neurosci Lett 2010, 484:12-16.
• [24]Aberg ND, Brywe KG, Isgaard J: Aspects of growth hormone and insulin-like growth factor-I related to neuroprotection, regeneration, and functional plasticity in the adult brain. ScientificWorldJournal 2006, 6:53-80.
• [25]Carro E, Trejo JL, Nunez A, Torres-Aleman I: Brain repair and neuroprotection by serum insulin-like growth factor I. Mol Neurobiol 2003, 27:153-162.
• [26]Sara VR, Carlsson-Skwirut C, Andersson C, Hall E, Sjogren B, Holmgren A, Jornvall H: Characterization of somatomedins from human fetal brain: identification of a variant form of insulin-like growth factor I. Proc Natl Acad Sci USA 1986, 83:4904-4907.
• [27]Guan J, Gluckman PD: IGF-1 derived small neuropeptides and analogues: a novel strategy for the development of pharmaceuticals for neurological conditions. Br J Pharmacol 2009, 157:881-891.
• [28]Ballard FJ, Wallace JC, Francis GL, Read LC, Tomas FM: Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I. Int J Biochem Cell Biol 1996, 28:1085-1087.
• [29]Carlsson-Skwirut C, Jornvall H, Holmgren A, Andersson C, Bergman T, Lundquist G, Sjogren B, Sara VR: Isolation and characterization of variant IGF-1 as well as IGF-2 from adult human brain. FEBS Lett 1986, 201:46-50.
• [30]Guan J, Thomas GB, Lin H, Mathai S, Bachelor DC, George S, Gluckman PD: Neuroprotective effects of the N-terminal tripeptide of insulin-like growth factor-1, glycine-proline-glutamate (GPE) following intravenous infusion in hypoxic-ischemic adult rats. Neuropharmacology 2004, 47:892-903.
• [31]Yamamoto H, Murphy LJ: Generation of des-(1-3) insulin-like growth factor-I in serum by an acid protease. Endocrinology 1994, 135:2432-2439.
• [32]Yamamoto H, Murphy LJ: Enzymatic conversion of IGF-I to des(1-3)IGF-I in rat serum and tissues: a further potential site of growth hormone regulation of IGF-I action. J Endocrinol 1995, 146:141-148.
• [33]Bourguignon JP, Alvarez Gonzalez ML, Gerard A, Franchimont P: Gonadotropin releasing hormone inhibitory autofeedback by subproducts antagonist at N-methyl-D-aspartate receptors: a model of autocrine regulation of peptide secretion. Endocrinology 1994, 134:1589-1592.
• [34]Bourguignon JP, Gerard A, Alvarez Gonzalez ML, Franchimont P: Acute suppression of gonadotropin-releasing hormone secretion by insulin-like growth factor I and subproducts: an age-dependent endocrine effect. Neuroendocrinology 1993, 58:525-530.
• [35]Guan J, Krishnamurthi R, Waldvogel HJ, Faull RL, Clark R, Gluckman P: N-terminal tripeptide of IGF-1 (GPE) prevents the loss of TH positive neurons after 6-OHDA induced nigral lesion in rats. Brain Res 2000, 859:286-292.
• [36]Sizonenko SV, Sirimanne ES, Williams CE, Gluckman PD: Neuroprotective effects of the N-terminal tripeptide of IGF-1, glycine-proline-glutamate, in the immature rat brain after hypoxic-ischemic injury. Brain Res 2001, 922:42-50.
• [37]Paxinos G, Franklin KBJ: The Mouse Brain in Stereotaxic Coordinates, Deluxe Edition of the Atlas. Second edition. London: Academic Press; 2001.
• [38]Rojo AI, Innamorato NG, Martin-Moreno AM, De Ceballos ML, Yamamoto M, Cuadrado A: Nrf2 regulates microglial dynamics and neuroinflammation in experimental Parkinson's disease. Glia 2010, 58:588-598.
• [39]Trejo JL, Llorens-Martin MV, Torres-Aleman I: The effects of exercise on spatial learning and anxiety-like behavior are mediated by an IGF-I-dependent mechanism related to hippocampal neurogenesis. Mol Cell Neurosci 2008, 37:402-411.
• [40]Duman CH, Schlesinger L, Terwilliger R, Russell DS, Newton SS, Duman RS: Peripheral insulin-like growth factor-I produces antidepressant-like behavior and contributes to the effect of exercise. Behav Brain Res 2009, 198:366-371.
• [41]Burgdorf J, Kroes RA, Beinfeld MC, Panksepp J, Moskal JR: Uncovering the molecular basis of positive affect using rough-and-tumble play in rats: a role for insulin-like growth factor I. Neuroscience 2010, 168:769-777.
• [42]Hoshaw BA, Malberg JE, Lucki I: Central administration of IGF-I and BDNF leads to long-lasting antidepressant-like effects. Brain Res 2005, 1037:204-208.
• [43]Hoshaw BA, Hill TI, Crowley JJ, Malberg JE, Khawaja X, Rosenzweig-Lipson S, Schechter LE, Lucki I: Antidepressant-like behavioral effects of IGF-I produced by enhanced serotonin transmission. Eur J Pharmacol 2008, 594:109-116.
• [44]Malberg JE, Platt B, Rizzo SJ, Ring RH, Lucki I, Schechter LE, Rosenzweig-Lipson S: Increasing the levels of insulin-like growth factor-I by an IGF binding protein inhibitor produces anxiolytic and antidepressant-like effects. Neuropsychopharmacology 2007, 32:2360-2368.
• [45]Sara VR, Carlsson-Skwirut C, Bergman T, Jornvall H, Roberts PJ, Crawford M, Hakansson LN, Civalero I, Nordberg A: Identification of Gly-Pro-Glu (GPE), the aminoterminal tripeptide of insulin-like growth factor 1 which is truncated in brain, as a novel neuroactive peptide. Biochem Biophys Res Commun 1989, 165:766-771.
• [46]Dantzer R: Cytokine-induced sickness behavior: mechanisms and implications. Ann N Y Acad Sci 2001, 933:222-234.
• [47]Aliaga EE, Mendoza I, Tapia-Arancibia L: Distinct subcellular localization of BDNF transcripts in cultured hypothalamic neurons and modification by neuronal activation. J Neural Transm 2009, 116:23-32.
• [48]Sakata K, Jin L, Jha S: Lack of promoter IV-driven BDNF transcription results in depression-like behavior. Genes Brain Behav 2010.
• [49]Calabrese F, Molteni R, Maj PF, Cattaneo A, Gennarelli M, Racagni G, Riva MA: Chronic duloxetine treatment induces specific changes in the expression of BDNF transcripts and in the subcellular localization of the neurotrophin protein. Neuropsychopharmacology 2007, 32:2351-2359.
• [50]Bourguignon J, Gerard A: Role of insulin-like growth factor binding proteins in limitation of IGF-I degradation into the N-methyl-D-aspartate receptor antagonist GPE: evidence from gonadotrophin-releasing hormone secretion in vitro at two developmental stages. Brain Res 1999, 847:247-252.
• [51]Nilsson-Hakansson L, Civalero I, Zhang X, Carlsson-Skwirut C, Sara VR, Nordberg A: Effects of IGF-1, truncated IGF-1 and the tripeptide Gly-Pro-Glu on acetylcholine release from parietal cortex of rat brain. Neuroreport 1993, 4:1111-1114.
• [52]Alonso De Diego SA, Gutierrez-Rodriguez M, Perez de Vega MJ, Gonzalez-Muniz R, Herranz R, Martin-Martinez M, Cenarruzabeitia E, Frechilla D, Del Rio J, Jimeno ML, Garcia-Lopez MT: The neuroprotective activity of GPE tripeptide analogues does not correlate with glutamate receptor binding affinity. Bioorg Med Chem Lett 2006, 16:3396-3400.
• [53]Escartin C, Boyer F, Bemelmans AP, Hantraye P, Brouillet E: Insulin growth factor-1 protects against excitotoxicity in the rat striatum. Neuroreport 2004, 15:2251-2254.
• [54]Alexi T, Hughes PE, van Roon-Mom WM, Faull RL, Williams CE, Clark RG, Gluckman PD: The IGF-I amino-terminal tripeptide glycine-proline-glutamate (GPE) is neuroprotective to striatum in the quinolinic acid lesion animal model of Huntington's disease. Exp Neurol 1999, 159:84-97.
• [55]Dantzer R, O'Connor JC, Lawson MA, Kelley KW: Inflammation-associated depression: from serotonin to kynurenine. Psychoneuroendocrinology 2011, 36:426-436.
• [56]Lestage J, Verrier D, Palin K, Dantzer R: The enzyme indoleamine 2,3-dioxygenase is induced in the mouse brain in response to peripheral administration of lipopolysaccharide and superantigen. Brain Behav Immun 2002, 16:596-601.
• [57]Maes M, Leonard BE, Myint AM, Kubera M, Verkerk R: The new '5-HT' hypothesis of depression: cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression. Prog Neuropsychopharmacol Biol Psychiatry 2011, 35:702-721.
• [58]Ball HJ, Yuasa HJ, Austin CJ, Weiser S, Hunt NH: Indoleamine 2,3-dioxygenase-2; a new enzyme in the kynurenine pathway. Int J Biochem Cell Biol 2009, 41:467-471.
• [59]Nishizawa H, Kato T, Ota S, Nishiyama S, Pryor-Koishi K, Suzuki M, Tsutsumi M, Inagaki H, Kurahashi H, Udagawa Y: Genetic variation in the indoleamine 2,3-dioxygenase gene in pre-eclampsia. Am J Reprod Immunol 2010, 64:68-76.
• [60]Akbarian S, Rios M, Liu RJ, Gold SJ, Fong HF, Zeiler S, Coppola V, Tessarollo L, Jones KR, Nestler EJ, et al.: Brain-derived neurotrophic factor is essential for opiate-induced plasticity of noradrenergic neurons. J Neurosci 2002, 22:4153-4162.
• [61]Castren E, Voikar V, Rantamaki T: Role of neurotrophic factors in depression. Curr Opin Pharmacol 2007, 7:18-21.
• [62]Castren E, Rantamaki T: The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity. Dev Neurobiol 2010, 70:289-297.
• [63]Bibollet-Bahena O, Cui QL, Almazan G: The insulin-like growth factor-1 axis and its potential as a therapeutic target in central nervous system (CNS) disorders. Cent Nerv Syst Agents Med Chem 2009, 9:95-109.
• [64]Torres-Aleman I: Toward a comprehensive neurobiology of IGF-I. Dev Neurobiol 2010, 70:384-396.
• [65]Guan J: Insulin-Like Growth Factor -1 (IGF-1) Derived Neuropeptides, a Novel Strategy for the Development of Pharmaceuticals for Managing Ischemic Brain Injury. CNS Neurosci Ther 2011, 17:250-255.
• [66]Reijnders CM, Koster JG, van Buul-Offers SC: Overexpression of human IGF-II mRNA in the brain of transgenic mice modulates IGFBP-2 gene expression in the medulla oblongata. J Endocrinol 2004, 182:445-455.
• [67]Niblock MM, Brunso-Bechtold JK, Lynch CD, Ingram RL, McShane T, Sonntag WE: Distribution and levels of insulin-like growth factor I mRNA across the life span in the Brown Norway x Fischer 344 rat brain. Brain Res 1998, 804:79-86.
• [68]Zhou X, Herman JP, Paden CM: Evidence that IGF-I acts as an autocrine/paracrine growth factor in the magnocellular neurosecretory system: neuronal synthesis and induction of axonal sprouting. Exp Neurol 1999, 159:419-432.