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Cited by 420Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersStress Responses and Cortisol

Monocyte trafficking to the brain with stress and inflammation: a novel axis of immune-to-brain communication that influences mood and behavior

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Wohleb, Eric S., McKim, Daniel B., Sheridan, John F., Godbout, Jonathan P.·2015·Frontiers in Neuroscience
DOI 10.3389/fnins.2014.00447PMC PMC4300916
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Abstract

HIGHLIGHTSPsychological stress activates neuroendocrine pathways that alter immune responses.Stress-induced alterations in microglia phenotype and monocyte priming leads to aberrant peripheral and central inflammation.Elevated pro-inflammatory cytokine levels caused by microglia activation and recruitment of monocytes to the brain contribute to development and persistent anxiety-like behavior.Mechanisms that mediate interactions between microglia, endothelial cells, and macrophages and how these contribute to changes in behavior are discussed.Sensitization of microglia and re-distribution of primed monocytes are implicated in re-establishment of anxiety-like behavior. Psychological stress causes physiological, immunological, and behavioral alterations in humans and rodents that can be maladaptive and negatively affect quality of life. Several lines of evidence indicate that psychological stress disrupts key functional interactions between the immune system and brain that ultimately affects mood and behavior. For example, activation of microglia, the resident innate immune cells of the brain, has been implicated as a key regulator of mood and behavior in the context of prolonged exposure to psychological stress. Emerging evidence implicates a novel neuroimmune circuit involving microglia activation and sympathetic outflow to the peripheral immune system that further reinforces stress-related behaviors by facilitating the recruitment of inflammatory monocytes to the brain. Evidence from various rodent models, including repeated social defeat (RSD), revealed that trafficking of monocytes to the brain promoted the establishment of anxiety-like behaviors following prolonged stress exposure. In addition, new evidence implicates monocyte trafficking from the spleen to the brain as key regulator of recurring anxiety following exposure to prolonged stress. The purpose of this review is to discuss mechanisms that cause stress-induced monocyte re-distribution in the brain and how dynamic interactions between microglia, endothelial cells, and brain macrophages lead to maladaptive behavioral responses.

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  • The apparent contradiction between PVH stimulation-induced monocyte retention and chronic stress effects may reflect different monocyte mobilization dynamics in acute stress or HPA activation versus chronic stress.

    “Although the effects of PVH neuron stimulation on monocyte retention by the bone marrow may seem to contradict those expected from studies of chronic stress, it is likely that these differences may arise from differences in monocyte mobilization dynamics during acute stress or HPA axis activation, compared to chronic stress70.”

    From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [70]

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  1. Afan A. M. Broome C. S. Nicholls S. E. Whetton A. D. Miyan J. A. (1997). Bone marrow innervation regulates cellular retention in the murine haemopoietic system. Br. J. Haematol. 98, 569– 577. 10.1046/j.1365-2141.1997.2733092.x 9332309 · DOI
  2. Ajmo C. T. Jr. Collier L. A. Leonardo C. C. Hall A. A. Green S. M. Womble T. A.. (2009). Blockade of adrenoreceptors inhibits the splenic response to stroke. Exp. Neurol. 218, 47– 55. 10.1016/j.expneurol.2009.03.044 19371742 PMC2720830 · DOI
  3. Ajmo C. T. Jr. Vernon D. O. Collier L. Hall A. A. Garbuzova-Davis S. Willing A.. (2008). The spleen contributes to stroke-induced neurodegeneration. J. Neurosci. Res. 86, 2227– 2234. 10.1002/jnr.21661 18381759 PMC2680137 · DOI
  4. An Y. Chen Q. Quan N. (2011). Interleukin-1 exerts distinct actions on different cell types of the brain in vitro. J. Inflamm. Res. 2011, 11– 20. 10.2147/JIR.S15357 22022205 PMC3196613 · DOI
  5. Ataka K. Asakawa A. Nagaishi K. Kaimoto K. Sawada A. Hayakawa Y.. (2013). Bone marrow-derived microglia infiltrate into the paraventricular nucleus of chronic psychological stress-loaded mice. PLoS ONE 8: e81744. 10.1371/journal.pone.0081744 24303068 PMC3841189 · DOI · Paper page
  6. Avitsur R. Stark J. L. Dhabhar F. S. Sheridan J. F. (2002). Social stress alters splenocyte phenotype and function. J. Neuroimmunol. 132, 66– 71. 10.1016/S0165-5728(02)00310-7 12417435 · DOI
  7. Avitsur R. Stark J. L. Sheridan J. F. (2001). Social stress induces glucocorticoid resistance in subordinate animals. Horm. Behav. 39, 247– 257. 10.1006/hbeh.2001.1653 11374910 · DOI · Paper page
  8. Bailey M. T. Avitsur R. Engler H. Padgett D. A. Sheridan J. F. (2004). Physical defeat reduces the sensitivity of murine splenocytes to the suppressive effects of corticosterone. Brain Behav. Immun. 18, 416– 424. 10.1016/j.bbi.2003.09.012 15265534 · DOI
  9. Bailey M. T. Dowd S. E. Galley J. D. Hufnagle A. R. Allen R. G. Lyte M. (2011). Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav. Immun. 25, 397– 407. 10.1016/j.bbi.2010.10.023 21040780 PMC3039072 · DOI · Paper page
  10. Bailey M. T. Engler H. Powell N. D. Padgett D. A. Sheridan J. F. (2007). Repeated social defeat increases the bactericidal activity of splenic macrophages through a Toll-like receptor-dependent pathway. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293, R1180– R1190. 10.1152/ajpregu.00307.2007 17596326 · DOI · Paper page
  11. Bailey M. T. Kierstein S. Sharma S. Spaits M. Kinsey S. G. Tliba O.. (2009a). Social stress enhances allergen-induced airway inflammation in mice and inhibits corticosteroid responsiveness of cytokine production. J. Immunol. 182, 7888– 7896. 10.4049/jimmunol.0800891 19494313 PMC2767120 · DOI
  12. Bailey M. T. Kinsey S. G. Padgett D. A. Sheridan J. F. Leblebicioglu B. (2009b). Social stress enhances IL-1beta and TNF-alpha production by Porphyromonas gingivalis lipopolysaccharide-stimulated CD11b+ cells. Physiol. Behav. 98, 351– 358. 10.1016/j.physbeh.2009.06.013 19560480 PMC2748391 · DOI
  13. Bechmann I. Priller J. Kovac A. Bontert M. Wehner T. Klett F. F.. (2001). Immune surveillance of mouse brain perivascular spaces by blood-borne macrophages. Eur. J. Neurosci. 14, 1651– 1658. 10.1046/j.0953-816x.2001.01793.x 11860459 · DOI
  14. Bian Y. Pan Z. Hou Z. Huang C. Li W. Zhao B. (2012). Learning, memory, and glial cell changes following recovery from chronic unpredictable stress. Brain Res. Bull. 88, 471– 476. 10.1016/j.brainresbull.2012.04.008 22537595 · DOI
  15. Blandino P. Jr. Barnum C. J. Deak T. (2006). The involvement of norepinephrine and microglia in hypothalamic and splenic IL-1beta responses to stress. J. Neuroimmunol. 173, 87– 95. 10.1016/j.jneuroim.2005.11.021 16386803 · DOI
  16. Blandino P. Jr. Barnum C. J. Solomon L. G. Larish Y. Lankow B. S. Deak T. (2009). Gene expression changes in the hypothalamus provide evidence for regionally-selective changes in IL-1 and microglial markers after acute stress. Brain Behav. Immun. 23, 958– 968. 10.1016/j.bbi.2009.04.013 19464360 · DOI · Paper page
  17. Boivin N. Menasria R. Gosselin D. Rivest S. Boivin G. (2012). Impact of deficiency in CCR2 and CX3CR1 receptors on monocytes trafficking in herpes simplex virus encephalitis. J. Gen. Virol. 93, 1294– 1304. 10.1099/vir.0.041046-0 22377584 · DOI
  18. Cole S. W. Conti G. Arevalo J. M. Ruggiero A. M. Heckman J. J. Suomi S. J. (2012). Transcriptional modulation of the developing immune system by early life social adversity. Proc. Natl. Acad. Sci. U.S.A. 109, 20578– 20583. 10.1073/pnas.1218253109 23184974 PMC3528538 · DOI · Paper page
  19. Curry J. M. Hanke M. L. Piper M. G. Bailey M. T. Bringardner B. D. Sheridan J. F.. (2010). Social disruption induces lung inflammation. Brain Behav. Immun. 24, 394– 402. 10.1016/j.bbi.2009.10.019 19903521 PMC2826531 · DOI
  20. Degos V. Vacas S. Han Z. van Rooijen N. Gressens P. Su H.. (2013). Depletion of bone marrow-derived macrophages perturbs the innate immune response to surgery and reduces postoperative memory dysfunction. Anesthesiology 118, 527– 536. 10.1097/ALN.0b013e3182834d94 23426204 PMC3779063 · DOI
  21. Dissing-Olesen L. LeDue J. M. Rungta R. L. Hefendehl J. K. Choi H. B. MacVicar B. A. (2014). Activation of neuronal NMDA receptors triggers transient ATP-mediated microglial process outgrowth. J. Neurosci. 34, 10511– 10527. 10.1523/JNEUROSCI.0405-14.2014 25100586 PMC6802598 · DOI · Paper page
  22. D'Mello C. Le T. Swain M. G. (2009). Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation. J. Neurosci. 29, 2089– 2102. 10.1523/JNEUROSCI.3567-08.2009 19228962 PMC6666330 · DOI · Paper page
  23. D'Mello C. Riazi K. Le T. Stevens K. M. Wang A. McKay D. M.. (2013). P-selectin-mediated monocyte-cerebral endothelium adhesive interactions link peripheral organ inflammation to sickness behaviors. J. Neurosci. 33, 14878– 14888. 10.1523/JNEUROSCI.1329-13.2013 24027287 PMC6705165 · DOI
  24. Dong-Newsom P. Powell N. D. Bailey M. T. Padgett D. A. Sheridan J. F. (2010). Repeated social stress enhances the innate immune response to a primary HSV-1 infection in the cornea and trigeminal ganglia of Balb/c mice. Brain Behav. Immun. 24, 273– 280. 10.1016/j.bbi.2009.10.003 19822203 PMC2818401 · DOI
  25. Donnelly D. J. Popovich P. G. (2008). Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp. Neurol. 209, 378– 388. 10.1016/j.expneurol.2007.06.009 17662717 PMC2692462 · DOI · Paper page
  26. Dutta P. Courties G. Wei Y. Leuschner F. Gorbatov R. Robbins C. S.. (2012). Myocardial infarction accelerates atherosclerosis. Nature 487, 325– 329. 10.1038/nature11260 22763456 PMC3401326 · DOI
  27. Engler H. Bailey M. T. Engler A. Sheridan J. F. (2004). Effects of repeated social stress on leukocyte distribution in bone marrow, peripheral blood and spleen. J. Neuroimmunol. 148, 106– 115. 10.1016/j.jneuroim.2003.11.011 14975591 · DOI · Paper page
  28. Engler H. Bailey M. T. Engler A. Stiner-Jones L. M. Quan N. Sheridan J. F. (2008). Interleukin-1 receptor type 1-deficient mice fail to develop social stress-associated glucocorticoid resistance in the spleen. Psychoneuroendocrinology 33, 108– 117. 10.1016/j.psyneuen.2007.10.007 18037570 PMC2701260 · DOI · Paper page
  29. Engler H. Engler A. Bailey M. T. Sheridan J. F. (2005). Tissue-specific alterations in the glucocorticoid sensitivity of immune cells following repeated social defeat in mice. J. Neuroimmunol. 163, 110– 119. 10.1016/j.jneuroim.2005.03.002 15885313 · DOI · Paper page
  30. Evans D. L. Charney D. S. Lewis L. Golden R. N. Gorman J. M. Krishnan K. R.. (2005). Mood disorders in the medically ill: scientific review and recommendations. Biol. Psychiatry 58, 175– 189. 10.1016/j.biopsych.2005.05.001 16084838 · DOI · Paper page
  31. Faust N. Varas F. Kelly L. M. Heck S. Graf T. (2000). Insertion of enhanced green fluorescent protein into the lysozyme gene creates mice with green fluorescent granulocytes and macrophages. Blood 96, 719– 726. 10887140
  32. Fitting C. Dhawan S. Cavaillon J. M. (2004). Compartmentalization of tolerance to endotoxin. J. Infect. Dis. 189, 1295– 1303. 10.1086/382657 15031800 · DOI
  33. Ford A. L. Goodsall A. L. Hickey W. F. Sedgwick J. D. (1995). Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared. J. Immunol. 154, 4309– 4321. 7722289
  34. Frank M. G. Baratta M. V. Sprunger D. B. Watkins L. R. Maier S. F. (2007a). Microglia serve as a neuroimmune substrate for stress-induced potentiation of CNS pro-inflammatory cytokine responses. Brain Behav. Immun. 21, 47– 59. 10.1016/j.bbi.2006.03.005 16647243 · DOI · Paper page
  35. Frank M. G. Der-Avakian A. Bland S. T. Watkins L. R. Maier S. F. (2007b). Stress-induced glucocorticoids suppress the antisense molecular regulation of FGF-2 expression. Psychoneuroendocrinology 32, 376– 384. 10.1016/j.psyneuen.2007.02.001 17383826 · DOI
  36. Freeman D. Thompson C. Vorontsova N. Dunn G. Carter L. A. Garety P.. (2013). Paranoia and post-traumatic stress disorder in the months after a physical assault: a longitudinal study examining shared and differential predictors. Psychol. Med. 43, 2673– 2684. 10.1017/S003329171300038X 23531413 PMC3821375 · DOI · Paper page
  37. Galea I. Bechmann I. Perry V. H. (2007). What is immune privilege (not)? Trends Immunol. 28, 12– 18. 10.1016/j.it.2006.11.004 17129764 · DOI · Paper page
  38. Geissmann F. Jung S. Littman D. R. (2003). Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19, 71– 82. 10.1016/S1074-7613(03)00174-2 12871640 · DOI
  39. Gilman S. E. Trinh N. H. Smoller J. W. Fava M. Murphy J. M. Breslau J. (2013). Psychosocial stressors and the prognosis of major depression: a test of Axis IV. Psychol. Med. 43, 303– 316. 10.1017/S0033291712001080 22640506 PMC3721739 · DOI
  40. Goshen I. Yirmiya R. (2009). Interleukin-1 (IL-1): a central regulator of stress responses. Front. Neuroendocrinol. 30, 30– 45. 10.1016/j.yfrne.2008.10.001 19017533 · DOI · Paper page
  41. Gould E. McEwen B. S. Tanapat P. Galea L. A. Fuchs E. (1997). Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J. Neurosci. 17, 2492– 2498. 9065509 PMC6573503
  42. Gould E. Tanapat P. McEwen B. S. Flugge G. Fuchs E. (1998). Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc. Natl. Acad. Sci. U.S.A. 95, 3168– 3171. 10.1073/pnas.95.6.3168 9501234 PMC19713 · DOI · Paper page
  43. Grisanti L. A. Evanson J. Marchus E. Jorissen H. Woster A. P. DeKrey W.. (2010). Pro-inflammatory responses in human monocytes are beta1-adrenergic receptor subtype dependent. Mol. Immunol. 47, 1244– 1254. 10.1016/j.molimm.2009.12.013 20116105 PMC2862727 · DOI
  44. Hamilton J. A. Achuthan A. (2013). Colony stimulating factors and myeloid cell biology in health and disease. Trends Immunol. 34, 81– 89. 10.1016/j.it.2012.08.006 23000011 · DOI · Paper page
  45. Harrison J. K. Jiang Y. Chen S. Xia Y. Maciejewski D. McNamara R. K.. (1998). Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc. Natl. Acad. Sci. U.S.A. 95, 10896– 10901. 10.1073/pnas.95.18.10896 9724801 PMC27992 · DOI · Paper page
  46. Hinwood M. Tynan R. J. Charnley J. L. Beynon S. B. Day T. A. Walker F. R. (2013). Chronic stress induced remodeling of the prefrontal cortex: structural re-organization of microglia and the inhibitory effect of minocycline. Cereb. Cortex 23, 1784– 1797. 10.1093/cercor/bhs151 22710611 · DOI
  47. Jezova D. Ochedalski T. Kiss A. Aguilera G. (1998). Brain angiotensin II modulates sympathoadrenal and hypothalamic pituitary adrenocortical activation during stress. J. Neuroendocrinol. 10, 67– 72. 10.1046/j.1365-2826.1998.00182.x 9510060 · DOI
  48. Johnson J. D. Campisi J. Sharkey C. M. Kennedy S. L. Nickerson M. Greenwood B. N.. (2005). Catecholamines mediate stress-induced increases in peripheral and central inflammatory cytokines. Neuroscience 135, 1295– 1307. 10.1016/j.neuroscience.2005.06.090 16165282 · DOI · Paper page
  49. Kang H. J. Voleti B. Hajszan T. Rajkowska G. Stockmeier C. A. Licznerski P.. (2012). Decreased expression of synapse-related genes and loss of synapses in major depressive disorder. Nat. Med. 18, 1413– 1417. 10.1038/nm.2886 22885997 PMC3491115 · DOI · Paper page
  50. Katayama Y. Battista M. Kao W. M. Hidalgo A. Peired A. J. Thomas S. A.. (2006). Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell 124, 407– 421. 10.1016/j.cell.2005.10.041 16439213 · DOI · Paper page
  51. Kerfoot S. M. D'Mello C. Nguyen H. Ajuebor M. N. Kubes P. Le T.. (2006). TNF-alpha-secreting monocytes are recruited into the brain of cholestatic mice. Hepatology 43, 154– 162. 10.1002/hep.21003 16374849 · DOI
  52. Kettenmann H. Hanisch U. K. Noda M. Verkhratsky A. (2011). Physiology of microglia. Physiol. Rev. 91, 461– 553. 10.1152/physrev.00011.2010 21527731 · DOI · Paper page
  53. Kierdorf K. Katzmarski N. Haas C. A. Prinz M. (2013). Bone marrow cell recruitment to the brain in the absence of irradiation or parabiosis bias. PLoS ONE 8: e58544. 10.1371/journal.pone.0058544 23526995 PMC3592806 · DOI
  54. Kigerl K. A. Gensel J. C. Ankeny D. P. Alexander J. K. Donnelly D. J. Popovich P. G. (2009). Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J. Neurosci. 29, 13435– 13444. 10.1523/JNEUROSCI.3257-09.2009 19864556 PMC2788152 · DOI · Paper page
  55. Kollack-Walker S. Watson S. J. Akil H. (1997). Social stress in hamsters: defeat activates specific neurocircuits within the brain. J. Neurosci. 17, 8842– 8855. 9348352 PMC6573068
  56. Koo J. W. Duman R. S. (2009). Interleukin-1 receptor null mutant mice show decreased anxiety-like behavior and enhanced fear memory. Neurosci. Lett. 456, 39– 43. 10.1016/j.neulet.2009.03.068 19429130 PMC3678367 · DOI
  57. Kopp B. L. Wick D. Herman J. P. (2013). Differential effects of homotypic vs. heterotypic chronic stress regimens on microglial activation in the prefrontal cortex. Physiol. Behav. 122, 246– 252. 10.1016/j.physbeh.2013.05.030 23707717 PMC3797875 · DOI
  58. Kovacs K. J. (1998). c-Fos as a transcription factor: a stressful (re)view from a functional map. Neurochem. Int. 33, 287– 297. 10.1016/S0197-0186(98)00023-0 9840219 · DOI · Paper page
  59. Krishnan V. Nestler E. J. (2008). The molecular neurobiology of depression. Nature 455, 894– 902. 10.1038/nature07455 18923511 PMC2721780 · DOI · Paper page
  60. Leuschner F. Rauch P. J. Ueno T. Gorbatov R. Marinelli B. Lee W. W.. (2012). Rapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis. J. Exp. Med. 209, 123– 137. 10.1084/jem.20111009 22213805 PMC3260875 · DOI
  61. Li Q. Powell N. Zhang H. Belevych N. Ching S. Chen Q.. (2012). Endothelial IL-1R1 is a critical mediator of EAE pathogenesis. Brain Behav. Immun. 25, 160– 167. 10.1016/j.bbi.2010.09.009 20854891 PMC2991628 · DOI
  62. Liezmann C. Stock D. Peters E. M. (2012). Stress induced neuroendocrine-immune plasticity: A role for the spleen in peripheral inflammatory disease and inflammaging? Dermatoendocrinol 4, 271– 279. 10.4161/derm.22023 23467333 PMC3583888 · DOI
  63. Magarinos A. M. McEwen B. S. Flugge G. Fuchs E. (1996). Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. J. Neurosci. 16, 3534– 3540. 8627386 PMC6579123
  64. Martinez M. Calvo-Torrent A. Herbert J. (2002). Mapping brain response to social stress in rodents with c-fos expression: a review. Stress 5, 3– 13. 10.1080/102538902900012369 12171762 · DOI
  65. Martinez M. Phillips P. J. Herbert J. (1998). Adaptation in patterns of c-fos expression in the brain associated with exposure to either single or repeated social stress in male rats. Eur. J. Neurosci. 10, 20– 33. 10.1046/j.1460-9568.1998.00011.x 9753110 · DOI
  66. Mays J. W. Bailey M. T. Hunzeker J. T. Powell N. D. Papenfuss T. Karlsson E. A.. (2010). Influenza virus-specific immunological memory is enhanced by repeated social defeat. J. Immunol. 184, 2014– 2025. 10.4049/jimmunol.0900183 20083672 PMC3066050 · DOI · Paper page
  67. McLaughlin K. A. Conron K. J. Koenen K. C. Gilman S. E. (2010). Childhood adversity, adult stressful life events, and risk of past-year psychiatric disorder: a test of the stress sensitization hypothesis in a population-based sample of adults. Psychol. Med. 40, 1647– 1658. 10.1017/S0033291709992121 20018126 PMC2891275 · DOI · Paper page
  68. Miller A. H. Maletic V. Raison C. L. (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol. Psychiatry 65, 732– 741. 10.1016/j.biopsych.2008.11.029 19150053 PMC2680424 · DOI · Paper page
  69. Miller G. E. Murphy M. L. Cashman R. Ma R. Ma J. Arevalo J. M.. (2014). Greater inflammatory activity and blunted glucocorticoid signaling in monocytes of chronically stressed caregivers. Brain Behav. Immun. 41, 191– 199. 10.1016/j.bbi.2014.05.016 25242587 PMC4973629 · DOI · Paper page
  70. Mitra R. Jadhav S. McEwen B. S. Vyas A. Chattarji S. (2005). Stress duration modulates the spatiotemporal patterns of spine formation in the basolateral amygdala. Proc. Natl. Acad. Sci. U.S.A. 102, 9371– 9376. 10.1073/pnas.0504011102 15967994 PMC1166638 · DOI · Paper page
  71. Mizoguchi K. Shoji H. Ikeda R. Tanaka Y. Tabira T. (2008). Persistent depressive state after chronic stress in rats is accompanied by HPA axis dysregulation and reduced prefrontal dopaminergic neurotransmission. Pharmacol. Biochem. Behav. 91, 170– 175. 10.1016/j.pbb.2008.07.002 18675292 · DOI
  72. Morilak D. A. Barrera G. Echevarria D. J. Garcia A. S. Hernandez A. Ma S.. (2005). Role of brain norepinephrine in the behavioral response to stress. Prog. Neuropsychopharmacol. Biol. Psychiatry. 29, 1214– 1224. 10.1016/j.pnpbp.2005.08.007 16226365 · DOI · Paper page
  73. Philbert J. Pichat P. Beeske S. Decobert M. Belzung C. Griebel G. (2011). Acute inescapable stress exposure induces long-term sleep disturbances and avoidance behavior: a mouse model of post-traumatic stress disorder (PTSD). Behav. Brain Res. 221, 149– 154. 10.1016/j.bbr.2011.02.039 21377492 · DOI · Paper page
  74. Pocock J. M. Kettenmann H. (2007). Neurotransmitter receptors on microglia. Trends Neurosci. 30, 527– 535. 10.1016/j.tins.2007.07.007 17904651 · DOI · Paper page
  75. Price J. L. Drevets W. C. (2010). Neural circuits underlying the pathophysiology of mood disorders. Trends Cogn. Sci. 16, 61– 71. 10.1016/j.tics.2011.12.011 22197477 · DOI · Paper page
  76. Prinz M. Priller J. (2010). Tickets to the brain: role of CCR2 and CX3CR1 in myeloid cell entry in the CNS. J. Neuroimmunol. 224, 80– 84. 10.1016/j.jneuroim.2010.05.015 20554025 · DOI · Paper page
  77. Quan N. Avitsur R. Stark J. L. He L. Lai W. Dhabhar F.. (2003). Molecular mechanisms of glucocorticoid resistance in splenocytes of socially stressed male mice. J. Neuroimmunol. 137, 51– 58. 10.1016/S0165-5728(03)00042-0 12667647 · DOI · Paper page
  78. Radley J. J. Rocher A. B. Rodriguez A. Ehlenberger D. B. Dammann M. McEwen B. S.. (2008). Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex. J. Comp. Neurol. 507, 1141– 1150. 10.1002/cne.21588 18157834 PMC2796421 · DOI
  79. Rohleder N. (2012). Acute and chronic stress induced changes in sensitivity of peripheral inflammatory pathways to the signals of multiple stress systems −2011 Curt Richter Award Winner. Psychoneuroendocrinology 37, 307– 316. 10.1016/j.psyneuen.2011.12.015 22226321 · DOI · Paper page
  80. Roozendaal B. McEwen B. S. Chattarji S. (2009). Stress, memory and the amygdala. Nat. Rev. Neurosci. 10, 423– 433. 10.1038/nrn2651 19469026 · DOI · Paper page
  81. Saavedra J. M. Ando H. Armando I. Baiardi G. Bregonzio C. Juorio A.. (2005). Anti-stress and anti-anxiety effects of centrally acting angiotensin II AT1 receptor antagonists. Regul. Pept. 128, 227– 238. 10.1016/j.regpep.2004.12.015 15837532 · DOI
  82. Saavedra J. M. Benicky J. (2007). Brain and peripheral angiotensin II play a major role in stress. Stress 10, 185– 193. 10.1080/10253890701350735 17514587 · DOI
  83. Samuels E. R. Szabadi E. (2008). Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part I: principles of functional organisation. Curr. Neuropharmacol. 6, 235– 253. 10.2174/157015908785777229 19506723 PMC2687936 · DOI
  84. Sapolsky R. M. (2003). Stress and plasticity in the limbic system. Neurochem. Res. 28, 1735– 1742. 10.1023/A:1026021307833 14584827 · DOI
  85. Sawada A. Niiyama Y. Ataka K. Nagaishi K. Yamakage M. Fujimiya M. (2014). Suppression of bone marrow-derived microglia in the amygdala improves anxiety-like behavior induced by chronic partial sciatic nerve ligation in mice. Pain 155, 1762– 1772. 10.1016/j.pain.2014.05.031 24907405 · DOI
  86. Schmidt M. V. Sterlemann V. Ganea K. Liebl C. Alam S. Harbich D.. (2007). Persistent neuroendocrine and behavioral effects of a novel, etiologically relevant mouse paradigm for chronic social stress during adolescence. Psychoneuroendocrinology 32, 417– 429. 10.1016/j.psyneuen.2007.02.011 17449187 · DOI
  87. Sedgwick J. D. Schwender S. Imrich H. Dorries R. Butcher G. W. ter Meulen V. (1991). Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Proc. Natl. Acad. Sci. U.S.A. 88, 7438– 7442. 10.1073/pnas.88.16.7438 1651506 PMC52311 · DOI
  88. Seifert H. A. Hall A. A. Chapman C. B. Collier L. A. Willing A. E. Pennypacker K. R. (2012). A transient decrease in spleen size following stroke corresponds to splenocyte release into systemic circulation. J. Neuroimmune Pharmacol. 7, 1017– 1024. 10.1007/s11481-012-9406-8 23054371 PMC3518577 · DOI
  89. Serbina N. V. Pamer E. G. (2006). Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat. Immunol. 7, 311– 317. 10.1038/ni1309 16462739 · DOI
  90. Serrats J. Schiltz J. C. Garcia-Bueno B. van Rooijen N. Reyes T. M. Sawchenko P. E. (2010). Dual roles for perivascular macrophages in immune-to-brain signaling. Neuron 65, 94– 106. 10.1016/j.neuron.2009.11.032 20152116 PMC2873837 · DOI · Paper page
  91. Sheehan T. P. Chambers R. A. Russell D. S. (2004). Regulation of affect by the lateral septum: implications for neuropsychiatry. Brain Res. Brain Res. Rev. 46, 71– 117. 10.1016/j.brainresrev.2004.04.009 15297155 · DOI · Paper page
  92. Sloan E. K. Capitanio J. P. Cole S. W. (2008). Stress-induced remodeling of lymphoid innervation. Brain Behav. Immun. 22, 15– 21. 10.1016/j.bbi.2007.06.011 17697764 PMC2754291 · DOI · Paper page
  93. Stanimirovic D. B. Friedman A. (2012). Pathophysiology of the neurovascular unit: disease cause or consequence? J. Cereb. Blood Flow Metab. 32, 1207– 1221. 10.1038/jcbfm.2012.25 22395208 PMC3390807 · DOI
  94. Stark J. L. Avitsur R. Hunzeker J. Padgett D. A. Sheridan J. F. (2002). Interleukin-6 and the development of social disruption-induced glucocorticoid resistance. J. Neuroimmunol. 124, 9– 15. 10.1016/S0165-5728(02)00004-8 11958817 · DOI · Paper page
  95. Stark J. L. Avitsur R. Padgett D. A. Campbell K. A. Beck F. M. Sheridan J. F. (2001). Social stress induces glucocorticoid resistance in macrophages. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280, R1799– R1805. 11353685
  96. Sternberg E. M. (2006). Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens. Nat. Rev. Immunol. 6, 318– 328. 10.1038/nri1810 16557263 PMC1783839 · DOI · Paper page
  97. Swirski F. K. Nahrendorf M. Etzrodt M. Wildgruber M. Cortez-Retamozo V. Panizzi P.. (2009). Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325, 612– 616. 10.1126/science.1175202 19644120 PMC2803111 · DOI · Paper page
  98. Tang Y. Shankar R. Gamelli R. Jones S. (1999). Dynamic norepinephrine alterations in bone marrow: evidence of functional innervation. J. Neuroimmunol. 96, 182– 189. 10.1016/S0165-5728(99)00032-6 10337916 · DOI
  99. Tarr A. J. Powell N. D. Reader B. F. Bhave N. S. Roloson A. L. Carson W. E. III Sheridan J. F. (2012). beta-Adrenergic receptor mediated increases in activation and function of natural killer cells following repeated social disruption. Brain Behav. Immun. 26, 1226– 1238. 10.1016/j.bbi.2012.07.002 22796551 PMC3468689 · DOI
  100. Terrando N. Eriksson L. I. Ryu J. K. Yang T. Monaco C. Feldmann M.. (2011). Resolving postoperative neuroinflammation and cognitive decline. Ann. Neurol. 70, 986– 995. 10.1002/ana.22664 22190370 PMC4556354 · DOI
  101. Torres-Platas S. G. Cruceanu C. Chen G. G. Turecki G. Mechawar N. (2014). Evidence for increased microglial priming and macrophage recruitment in the dorsal anterior cingulate white matter of depressed suicides. Brain Behav. Immun. 42, 50– 59. 10.1016/j.bbi.2014.05.007 24858659 · DOI · Paper page
  102. Tremblay M. E. Stevens B. Sierra A. Wake H. Bessis A. Nimmerjahn A. (2011). The role of microglia in the healthy brain. J. Neurosci. 31, 16064– 16069. 10.1523/JNEUROSCI.4158-11.2011 22072657 PMC6633221 · DOI · Paper page
  103. Tynan R. J. Naicker S. Hinwood M. Nalivaiko E. Buller K. M. Pow D. V.. (2010). Chronic stress alters the density and morphology of microglia in a subset of stress-responsive brain regions. Brain Behav. Immun. 24, 1058– 1068. 10.1016/j.bbi.2010.02.001 20153418 · DOI · Paper page
  104. Udina M. Moreno-Espana J. Capuron L. Navines R. Farre M. Vieta E.. (2014). Cytokine-induced depression: current status and novel targets for depression therapy. CNS Neurol. Disord. Drug Targets 13, 1066– 1074. 10.2174/1871527313666140612121921 24923336 · DOI
  105. Varvel N. H. Grathwohl S. A. Baumann F. Liebig C. Bosch A. Brawek B.. (2012). Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells. Proc. Natl. Acad. Sci. U.S.A. 109, 18150– 18155. 10.1073/pnas.1210150109 23071306 PMC3497743 · DOI
  106. Vyas A. Bernal S. Chattarji S. (2003). Effects of chronic stress on dendritic arborization in the central and extended amygdala. Brain Res. 965, 290– 294. 10.1016/S0006-8993(02)04162-8 12591150 · DOI · Paper page
  107. Walker W. S. (1999). Separate precursor cells for macrophages and microglia in mouse brain: immunophenotypic and immunoregulatory properties of the progeny. J. Neuroimmunol. 94, 127– 133. 10.1016/S0165-5728(98)00237-9 10376945 · DOI
  108. Wohleb E. S. Fenn A. M. Pacenta A. M. Powell N. D. Sheridan J. F. Godbout J. P. (2012). Peripheral innate immune challenge exaggerated microglia activation, increased the number of inflammatory CNS macrophages, and prolonged social withdrawal in socially defeated mice. Psychoneuroendocrinology 37, 1491– 1505. 10.1016/j.psyneuen.2012.02.003 22386198 PMC3368999 · DOI · Paper page
  109. Wohleb E. S. Godbout J. P. (2013). Basic aspects of the immunology of neuroinflammation. Mod. Trends Pharmacopsychiatry 28, 1– 19. 10.1159/000343964 25224887 · DOI
  110. Wohleb E. S. Hanke M. L. Corona A. W. Powell N. D. Stiner L. M. Bailey M. T.. (2011). β-Adrenergic receptor antagonism prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat. J. Neurosci. 31, 6277– 6288. 10.1523/JNEUROSCI.0450-11.2011 21525267 PMC3160240 · DOI · Paper page
  111. Wohleb E. S. McKim D. B. Shea D. T. Powell N. D. Tarr A. J. Sheridan J. F.. (2014a). Re-establishment of anxiety in stress-sensitized mice is caused by monocyte trafficking from the spleen to the brain. Biol. Psychiatry 75, 970– 981. 10.1016/j.biopsych.2013.11.029 24439304 PMC4084643 · DOI · Paper page
  112. Wohleb E. S. Powell N. D. Godbout J. P. Sheridan J. F. (2013). Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes anxiety-like behavior. J. Neurosci. 33, 13820– 13833. 10.1523/JNEUROSCI.1671-13.2013 23966702 PMC3755721 · DOI · Paper page
  113. Yalcin I. Aksu F. Belzung C. (2005). Effects of desipramine and tramadol in a chronic mild stress model in mice are altered by yohimbine but not by pindolol. Eur. J. Pharmacol. 514, 165– 174. 10.1016/j.ejphar.2005.03.029 15910803 · DOI

Cited by

Sorted by citations

Authors
Wohleb, E. S., McKim, D. B., Sheridan, J. F., & Godbout, J. P.
Affiliations
  • Yale University (US)
  • The Ohio State University (US)
Corresponding author
Godbout, Jonathan P.
ORCID
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2015-01-21
Volume
8
Pages
447-447
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2014.00447
PMC
PMC4300916
OpenAlex
W2043299701
Cited by
420
References
54
Citations by year
2026: 19 · 2025: 28 · 2024: 33 · 2023: 39 · 2022: 46 · 2021: 46 · 2020: 41 · 2019: 47 · 2018: 32 · 2017: 39 · 2016: 29 · 2015: 19
FWCI
3.16
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute on Aging (R01AG033028)
  • National Institute of Mental Health (R01MH097243, R01-AG033028, R01MH093473, R01-MH-093472)
  • National Institute of Dental and Craniofacial Research (DE-014320, T32DE014320)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
monocyte trafficking, psychological stress, neuroinflammation, microglial activation, anxiety-like behavior, inflammatory cytokines, repeated social defeat, brain macrophages, endothelial cells, sympathetic nervous system, mood and behavior

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