Inflammation early in life is a vulnerability factor for emotional behavior at adolescence and for lipopolysaccharide-induced spatial memory and neurogenesis alteration at adulthood

Journal of Neuroinflammation

Sophie Layé²  Pascale Le Ruyet¹  Aline Foury²  Agnes Aubert²  Pierre Trifilieff²  Corinne Joffre²  Anne-Laure Dinel² 

[1] Lactalis, R&D, Retiers F-35240, France;University of Bordeaux, Bordeaux, France

关键词: adulthood;    adolescence;    neurogenesis;    cognition;    depression;    anxiety;    perinatal;    cytokines;    lipopolysaccharide;   

Others  :  1150727
DOI  :  10.1186/s12974-014-0155-x

 received in 2014-04-09, accepted in 2014-08-21,  发布年份 2014

【 摘 要 】

Background

The postnatal period is a critical time window during which inflammatory events have significant and enduring effects on the brain, and as a consequence, induce alterations of emotional behavior and/or cognition later in life. However, the long-term effect of neonatal inflammation on behavior during adolescence, a sensitive period for the development of neurodevelopmental psychiatric disorders, has been little studied. In this study, we examined whether an early-life inflammatory challenge could alter emotional behaviors and spatial memory at adolescence and adulthood and whether stress axis activity, inflammatory response and neurogenesis were affected.

Methods

Lipopolysaccharide (LPS, 100 ?g/kg) was administered to mice on postnatal day (PND) 14 and cytokine expression was measured in the plasma and in brain structures 3 hours later. Anxiety-like and depressive-like behavior (measured in the novelty-suppressed feeding test and the forced swim test, respectively) and spatial memory (Y-maze test) were measured at adolescence (PND30) and adulthood (PND90). Hypothalamic-pituitary-adrenal (HPA) axis activity (plasma corticosterone and glucocorticoid receptors in the hippocampus and prefrontal cortex) was measured at adulthood. In addition, the impact of a novel adult LPS challenge (100 ?/kg) was measured on spatial memory (Y-maze test), neurogenesis (doublecortin-positive cell numbers in the hippocampus) and plasma cytokine expression.

Results

First, we show in PND14 pups that a peripheral administration of LPS induced the expression of pro- and anti-inflammatory cytokines in the plasma and brain structures that were studied 3 hours after administration. Anxiety-like behavior was altered in adolescent, but not in adult, mice, whereas depressive-like behavior was spared at adolescence and increased at adulthood. This was accompanied by a decreased phosphorylation of the glucocorticoid receptor in the prefrontal cortex, with no effect on corticosterone levels. Second, neonatal LPS treatment had no effect on spatial memory in adolescence and adulthood. However, a second challenge of LPS in adulthood impaired spatial memory performance and neurogenesis and increased circulating levels of CCL2.

Conclusions

Our study shows for the first time, in mice, that a peripheral LPS treatment at PND14 differentially alters emotional behaviors, but not spatial memory, at adolescence and adulthood. The behavioral effect of LPS at PND14 could be attributed to HPA axis deregulation and neurogenesis impairment.

【 授权许可】

   
2014 Dinel et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Karrow NA: Activation of the hypothalamic-pituitary-adrenal axis and autonomic nervous system during inflammation and altered programming of the neuroendocrine-immune axis during fetal and neonatal development: lessons learned from the model inflammagen, lipopolysaccharide. Brain Behav Immun 2006, 20:144-158.
• [2]Gilmore JH, Jarskog LF: Exposure to infection and brain development: cytokines in the pathogenesis of schizophrenia. Schizophr Res 1997, 24:365-367.
• [3]Boksa P: Effects of prenatal infection on brain development and behavior: a review of findings from animal models. Brain Behav Immun 2010, 24:881-897.
• [4]Sominsky L, Fuller EA, Bondarenko E, Ong LK, Averell L, Nalivaiko E, Dunkley PR, Dickson PW, Hodgson DM: Functional programming of the autonomic nervous system by early life immune exposure: implications for anxiety. PLoS One 2013, 8:e57700.
• [5]Tenk CM, Kavaliers M, Ossenkopp KP: Neonatal treatment with lipopolysaccharide differentially affects adult anxiety responses in the light¿dark test and taste neophobia test in male and female rats. Int J Dev Neurosci 2013, 31:171-180.
• [6]Spencer SJ, Galic MA, Pittman QJ: Neonatal programming of innate immune function. Am J Physiol Endocrinol Metab 2011, 300:E11-E18.
• [7]Schwarz JM, Bilbo SD: LPS elicits a much larger and broader inflammatory response than Escherichia coli infection within the hippocampus of neonatal rats. Neurosci Lett 2011, 497:110-115.
• [8]Bilbo SD, Levkoff LH, Mahoney JH, Watkins LR, Rudy JW, Maier SF: Neonatal infection induces memory impairments following an immune challenge in adulthood. Behav Neurosci 2005, 119:293-301.
• [9]Arsenault D, St-Amour I, Cisbani G, Rousseau LS, Cicchetti F: The different effects of LPS and poly I:C prenatal immune challenges on the behavior, development and inflammatory responses in pregnant mice and their offspring. Brain Behav Immun 2014, 38:77-90.
• [10]Bingham BC, Sheela Rani CS, Frazer A, Strong R, Morilak DA: Exogenous prenatal corticosterone exposure mimics the effects of prenatal stress on adult brain stress response systems and fear extinction behavior. Psychoneuroendocrinology 2013, 38:2746-2757.
• [11]Smith PL, Hagberg H, Naylor AS, Mallard C: Neonatal peripheral immune challenge activates microglia and inhibits neurogenesis in the developing murine hippocampus. Dev Neurosci 2014, 36:119-131.
• [12]Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, Ragozzino D, Gross CT: Synaptic pruning by microglia is necessary for normal brain development. Science 2011, 333:1456-1458.
• [13]Zhan Y, Paolicelli RC, Sforazzini F, Weinhard L, Bolasco G, Pagani F, Vyssotski AL, Bifone A, Gozzi A, Ragozzino D, Gross CT: Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat Neurosci 2014, 17:400-406.
• [14]Schmidt MV, Enthoven L, van der Mark M, Levine S, de Kloet ER, Oitzl MS: The postnatal development of the hypothalamic-pituitary-adrenal axis in the mouse. Int J Dev Neurosci 2003, 21:125-132.
• [15]Dent GW, Smith MA, Levine S: The ontogeny of the neuroendocrine response to endotoxin. Brain Res Dev Brain Res 1999, 117:21-29.
• [16]Shanks N, Larocque S, Meaney MJ: Neonatal endotoxin exposure alters the development of the hypothalamic-pituitary-adrenal axis: early illness and later responsivity to stress. J Neurosci 1995, 15:376-384.
• [17]Walker FR, Knott B, Hodgson DM: Neonatal endotoxin exposure modifies the acoustic startle response and circulating levels of corticosterone in the adult rat but only following acute stress. J Psychiatr Res 2008, 42:1094-1103.
• [18]Spencer SJ, Boisse L, Mouihate A, Pittman QJ: Long term alterations in neuroimmune responses of female rats after neonatal exposure to lipopolysaccharide. Brain Behav Immun 2006, 20:325-330.
• [19]Mouihate A, Galic MA, Ellis SL, Spencer SJ, Tsutsui S, Pittman QJ: Early life activation of toll-like receptor 4 reprograms neural anti-inflammatory pathways. J Neurosci 2010, 30:7975-7983.
• [20]Ellis S, Mouihate A, Pittman QJ: Neonatal programming of the rat neuroimmune response: stimulus specific changes elicited by bacterial and viral mimetics. J Physiol 2006, 571:695-701.
• [21]Gilmore WJ, Hartmann G, Piquette-Miller M, Marriott J, Kirby GM: Effects of lipopolysaccharide-stimulated inflammation and pyrazole-mediated hepatocellular injury on mouse hepatic Cyp2a5 expression. Toxicology 2003, 184:211-226.
• [22]Zuckerman L, Weiner I: Maternal immune activation leads to behavioral and pharmacological changes in the adult offspring. J Psychiatr Res 2005, 39:311-323.
• [23]Bilbo SD, Biedenkapp JC, Der-Avakian A, Watkins LR, Rudy JW, Maier SF: Neonatal infection-induced memory impairment after lipopolysaccharide in adulthood is prevented via caspase-1 inhibition. J Neurosci 2005, 25:8000-8009.
• [24]Boisse L, Spencer SJ, Mouihate A, Vergnolle N, Pittman QJ: Neonatal immune challenge alters nociception in the adult rat. Pain 2005, 119:133-141.
• [25]Williamson LL, Sholar PW, Mistry RS, Smith SH, Bilbo SD: Microglia and memory: modulation by early-life infection. J Neurosci 2011, 31:15511-15521.
• [26]Bilbo SD, Schwarz JM: Early-life programming of later-life brain and behavior: a critical role for the immune system. Front Behav Neurosci 2009, 3:14.
• [27]Bilbo SD, Rudy JW, Watkins LR, Maier SF: A behavioural characterization of neonatal infection-facilitated memory impairment in adult rats. Behav Brain Res 2006, 169:39-47.
• [28]Anderson WF: Puberty and genetic susceptibility to breast cancer. N Engl J Med 2003, 349:1088-1089.
• [29]Spear LP: The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 2000, 24:417-463.
• [30]Sisk CL, Zehr JL: Pubertal hormones organize the adolescent brain and behavior. Front Neuroendocrinol 2005, 26:163-174.
• [31]Foley KA, Ossenkopp KP, Kavaliers M, Macfabe DF: Pre- and neonatal exposure to lipopolysaccharide or the enteric metabolite, propionic acid, alters development and behavior in adolescent rats in a sexually dimorphic manner. PLoS One 2014, 9:e87072.
• [32]Bilbo SD, Schwarz JM: The immune system and developmental programming of brain and behavior. Front Neuroendocrinol 2012, 33:267-286.
• [33]Spencer SJ, Heida JG, Pittman QJ: Early life immune challenge¿effects on behavioural indices of adult rat fear and anxiety. Behav Brain Res 2005, 164:231-238.
• [34]Guilloux JP, David DJ, Xia L, Nguyen HT, Rainer Q, Guiard BP, Reperant C, Deltheil T, Toth M, Hen R, Gardier AM: Characterization of 5-HT(1A/1B)?/?mice: an animal model sensitive to anxiolytic treatments. Neuropharmacology 2011, 61:478-488.
• [35]Moreau M, Andre C, O'Connor JC, Dumich SA, Woods JA, Kelley KW, Dantzer R, Lestage J, Castanon N: Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior. Brain Behav Immun 2008, 22:1087-1095.
• [36]Dinel AL, Andre C, Aubert A, Ferreira G, Laye S, Castanon N: Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome. PLoS One 2011, 6:e24325.
• [37]Dellu F, Contarino A, Simon H, Koob GF, Gold LH: Genetic differences in response to novelty and spatial memory using a two-trial recognition task in mice. Neurobiol Learn Mem 2000, 73:31-48.
• [38]Brown JP, Couillard-Despres S, Cooper-Kuhn CM, Winkler J, Aigner L, Kuhn HG: Transient expression of doublecortin during adult neurogenesis. J Comp Neurol 2003, 467:1-10.
• [39]Boitard C, Etchamendy N, Sauvant J, Aubert A, Tronel S, Marighetto A, Laye S, Ferreira G: Juvenile, but not adult exposure to high-fat diet impairs relational memory and hippocampal neurogenesis in mice. Hippocampus 2012, 22:2095-2100.
• [40]Gautron L, De Smedt-Peyrusse V, Laye S: Characterization of STAT3-expressing cells in the postnatal rat brain. Brain Res 2006, 1098:26-32.
• [41]Richard EM, Helbling JC, Tridon C, Desmedt A, Minni AM, Cador M, Pourtau L, Konsman JP, Mormede P, Moisan MP: Plasma transcortin influences endocrine and behavioral stress responses in mice. Endocrinology 2010, 151:649-659.
• [42]Labrousse VF, Costes L, Aubert A, Darnaudery M, Ferreira G, Amedee T, Laye S: Impaired interleukin-1beta and c-Fos expression in the hippocampus is associated with a spatial memory deficit in P2X(7) receptor-deficient mice. PLoS One 2009, 4:e6006.
• [43]Vukovic J, Borlikova GG, Ruitenberg MJ, Robinson GJ, Sullivan RK, Walker TL, Bartlett PF: Immature doublecortin-positive hippocampal neurons are important for learning but not for remembering. J Neurosci 2013, 33:6603-6613.
• [44]Koehl M, Abrous DN: A new chapter in the field of memory: adult hippocampal neurogenesis. Eur J Neurosci 2011, 33:1101-1114.
• [45]Lynch MA: Age-related impairment in long-term potentiation in hippocampus: a role for the cytokine, interleukin-1 beta? Prog Neurobiol 1998, 56:571-589.
• [46]Westin K, Buchhave P, Nielsen H, Minthon L, Janciauskiene S, Hansson O: CCL2 is associated with a faster rate of cognitive decline during early stages of Alzheimer's disease. PLoS One 2012, 7:e30525.
• [47]Laye S, Parnet P, Goujon E, Dantzer R: Peripheral administration of lipopolysaccharide induces the expression of cytokine transcripts in the brain and pituitary of mice. Brain Res Mol Brain Res 1994, 27:157-162.
• [48]Mingam R, Moranis A, Bluthe RM, De Smedt-Peyrusse V, Kelley KW, Guesnet P, Lavialle M, Dantzer R, Laye S: Uncoupling of interleukin-6 from its signalling pathway by dietary n-3-polyunsaturated fatty acid deprivation alters sickness behaviour in mice. Eur J Neurosci 2008, 28:1877-1886.
• [49]Banchereau J, Pascual V, O'Garra A: From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines. Nat Immunol 2012, 13:925-931.
• [50]Strle K, Zhou JH, Shen WH, Broussard SR, Johnson RW, Freund GG, Dantzer R, Kelley KW: Interleukin-10 in the brain. Crit Rev Immunol 2001, 21:427-449.
• [51]Bluthe RM, Castanon N, Pousset F, Bristow A, Ball C, Lestage J, Michaud B, Kelley KW, Dantzer R: Central injection of IL-10 antagonizes the behavioural effects of lipopolysaccharide in rats. Psychoneuroendocrinology 1999, 24:301-311.
• [52]Kelly A, Vereker E, Nolan Y, Brady M, Barry C, Loscher CE, Mills KH, Lynch MA: Activation of p38 plays a pivotal role in the inhibitory effect of lipopolysaccharide and interleukin-1 beta on long term potentiation in rat dentate gyrus. J Biol Chem 2003, 278:19453-19462.
• [53]Lynch AM, Walsh C, Delaney A, Nolan Y, Campbell VA, Lynch MA: Lipopolysaccharide-induced increase in signalling in hippocampus is abrogated by IL-10¿a role for IL-1 beta? J Neurochem 2004, 88:635-646.
• [54]Chen J, Liu X: The role of interferon gamma in regulation of CD4+ T-cells and its clinical implications. Cell Immunol 2009, 254:85-90.
• [55]Maher FO, Martin DS, Lynch MA: Increased IL-1beta in cortex of aged rats is accompanied by downregulation of ERK and PI-3 kinase. Neurobiol Aging 2004, 25:795-806.
• [56]Murray CA, Lynch MA: Evidence that increased hippocampal expression of the cytokine interleukin-1 beta is a common trigger for age- and stress-induced impairments in long-term potentiation. J Neurosci 1998, 18:2974-2981.
• [57]Lucchina L, Carola V, Pitossi F, Depino AM: Evaluating the interaction between early postnatal inflammation and maternal care in the programming of adult anxiety and depression-related behaviors. Behav Brain Res 2010, 213:56-65.
• [58]Walker FR, March J, Hodgson DM: Endotoxin exposure in early life alters the development of anxiety-like behaviour in the Fischer 344 rat. Behav Brain Res 2004, 154:63-69.
• [59]Doosti MH, Bakhtiari A, Zare P, Amani M, Majidi-Zolbanin N, Babri S, Salari AA: Impacts of early intervention with fluoxetine following early neonatal immune activation on depression-like behaviors and body weight in mice. Prog Neuropsychopharmacol Biol Psychiatry 2013, 43:55-65.
• [60]Spencer SJ, Martin S, Mouihate A, Pittman QJ: Early-life immune challenge: defining a critical window for effects on adult responses to immune challenge. Neuropsychopharmacology 2006, 31:1910-1918.
• [61]Boisse L, Mouihate A, Ellis S, Pittman QJ: Long-term alterations in neuroimmune responses after neonatal exposure to lipopolysaccharide. J Neurosci 2004, 24:4928-4934.
• [62]Galic MA, Riazi K, Heida JG, Mouihate A, Fournier NM, Spencer SJ, Kalynchuk LE, Teskey GC, Pittman QJ: Postnatal inflammation increases seizure susceptibility in adult rats. J Neurosci 2008, 28:6904-6913.
• [63]Feleder C, Tseng KY, Calhoon GG, O'Donnell P: Neonatal intrahippocampal immune challenge alters dopamine modulation of prefrontal cortical interneurons in adult rats. Biol Psychiatry 2010, 67:386-392.
• [64]Baumeister D, Lightman SL, Pariante CM: The Interface of Stress and the HPA Axis in Behavioural Phenotypes of Mental Illness.Curr Top Behav Neurosci 2014, [Epub ahead of print].
• [65]Holsboer F: The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 2000, 23:477-501.
• [66]Chrousos GP, Kino T: Glucocorticoid action networks and complex psychiatric and/or somatic disorders. Stress 2007, 10:213-219.
• [67]McKlveen JM, Myers B, Flak JN, Bundzikova J, Solomon MB, Seroogy KB, Herman JP: Role of prefrontal cortex glucocorticoid receptors in stress and emotion. Biol Psychiatry 2013, 74:672-679.
• [68]Anacker C, Zunszain PA, Cattaneo A, Carvalho LA, Garabedian MJ, Thuret S, Price J, Pariante CM: Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor. Mol Psychiatry 2011, 16:738-750.
• [69]Pace TW, Hu F, Miller AH: Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun 2007, 21:9-19.
• [70]Miller AH, Pariante CM, Pearce BD: Effects of cytokines on glucocorticoid receptor expression and function. Glucocorticoid resistance and relevance to depression. Adv Exp Med Biol 1999, 461:107-116.
• [71]Bastos GN, Moriya T, Inui F, Katura T, Nakahata N: Involvement of cyclooxygenase-2 in lipopolysaccharide-induced impairment of the newborn cell survival in the adult mouse dentate gyrus. Neuroscience 2008, 155:454-462.
• [72]Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O: Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci U S A 2003, 100:13632-13637.
• [73]Monje ML, Toda H, Palmer TD: Inflammatory blockade restores adult hippocampal neurogenesis. Science 2003, 302:1760-1765.
• [74]Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Després S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, Wyss-Coray T: The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 2011, 477:90-94.