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Learned Immunosuppression: Extinction, Renewal, and the Challenge of Reconsolidation

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Abstract

Behavioral conditioning of immune responses is one of the most impressive examples for the bidirectional communication among the nervous and immune systems. We established a model of behaviorally conditioned immunosuppression employing a conditioned taste aversion (CTA) paradigm in the rat pairing a novel taste (saccharin) as a conditioned stimulus (CS) with the immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US). By re-presenting the CS during evocation, rats avoid drinking the saccharin. Concomitantly animals display an immunosuppression reflected by an ex vivo reduction in splenic T cell proliferation as well as diminished interleukin-2 and interferon-γ production and cytokine mRNA expression, mimicking the actual effect of the US (CsA). Due to the fact that the kinetics of this behaviorally conditioned immunosuppression are completely unknown, extinction of the conditioned response on the behavioral level (CTA) as well as in the immune response needs to be elucidated together with the neural processes mediating the extinction process.

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References

  • Acosta JI, Thiel KJ, Sanabria F, Browning JR, Neisewander JL (2008) Effect of schedule of reinforcement on cue-elicited reinstatement of cocaine-seeking behavior. Behav Pharmacol 19:129–136

    Article  PubMed  CAS  Google Scholar 

  • Ader R (2003) Conditioned immunomodulation: research needs and directions. Brain Behav Immun 17:51–57

    Article  Google Scholar 

  • Ader R, Cohen N (1975) Behaviorally conditioned immunosuppression. Psychosom Med 37:333–340

    PubMed  CAS  Google Scholar 

  • Ader R, Cohen N (1982) Behaviorally conditioned immunosuppression and murine systemic lupus erythematosus. Science 215:1534–1536

    Article  PubMed  CAS  Google Scholar 

  • Ader R, Mercurio MG, Walton J, James D, Davis M, Ojha V, Kimball AB, Fiorentino D (2010) Conditioned pharmacotherapeutic effects: a preliminary study. Psychosom Med 72:192–197

    Article  PubMed  Google Scholar 

  • Bahar A, Dorfman N, Dudai Y (2004) Amygdalar circuits required for either consolidation or extinction of taste aversion memory are not required for reconsolidation. Eur J Neurosci 19:1115–1118

    Article  PubMed  Google Scholar 

  • Banks WA (2005) Blood–brain barrier transport of cytokines: a mechanism for neuro-pathology. Curr Pharm Des 11:973–984

    Article  PubMed  CAS  Google Scholar 

  • Batiuk TD, Halloran PF (1997) The downstream consequences of calcineurin inhibition. Transplan Proc 29:1239–1240

    Article  CAS  Google Scholar 

  • Berman DE, Dudai Y (2001) Memory extinction, learning anew, and learning the new: dissociations in the molecular machinery of learning in cortex. Science 291:2417–2419

    Article  PubMed  CAS  Google Scholar 

  • Berman DE, Hazvi S, Stehberg J, Bahar A, Dudai Y (2003) Conflicting processes in the extinction of conditioned taste aversion: behavioral and molecular aspects of latency, apparent stagnation, and spontaneous recovery. Learn Mem 10:16–25

    Article  PubMed  Google Scholar 

  • Bermúdez-Rattoni F (2004) Molecular mechanisms of taste-recognition memory. Nat Rev Neurosci 5:209–217

    Article  PubMed  Google Scholar 

  • Bermúdez-Rattoni F, McGaugh JL (1991) Insular cortex and amygdala lesions differentially affect acquisition on inhibitory avoidance and conditioned taste aversion. Brain Res 549:165–170

    Article  PubMed  Google Scholar 

  • Blalock JE, Smith EM (2007) Conceptual development of the immune system as a sixth sense. Brain Behav Immun 21:23–33

    Article  PubMed  CAS  Google Scholar 

  • Bouton ME, Westbrook RF, Corcoran KA, Maren S (2006) Contextual and temporal modulation of extinction: behavioral and biological mechanisms. Biol Psychiatry 60:352–360

    Article  PubMed  Google Scholar 

  • Bovbjerg D (2003) Conditioning, cancer, and immune regulation. Brain Behav Immun 17:58–S61

    Article  Google Scholar 

  • Brynskikh A, Warren T, Zhu J, Kipnis J (2008) Adaptive immunity affects learning behavior in mice. Brain Behav Immun 22:861–869

    Article  PubMed  CAS  Google Scholar 

  • Buske-Kirschbaum A, Kirschbaum C, Stierle H, Lehnert H, Hellhammer D (1992) Conditioned increase of natural killer cell activity (NKCA) in humans. Psychosom Med 54:123–132

    PubMed  CAS  Google Scholar 

  • Cefalu WT, Pardridge WM (1985) Restrictive transport of a lipid-soluble peptide (Cyclosporin) through the blood-brain-barrier. J Neurochem 45:1954–1956

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Lin W, Wang W, Shao F, Yang J, Wang B, Kuang F, Duan X, Ju G (2004) Enhancement of antibody production and expression of c-Fos in the insular cortex in response to a conditioned stimulus after a single-trial learning paradigm. Behav Brain Res 154:557–565

    Article  PubMed  CAS  Google Scholar 

  • Colloca L, Benedetti F (2005) Placebos and painkillers: is mind as real as matter? Nature Rev 6:545–552

    Article  CAS  Google Scholar 

  • Cubero I, Thiele TE, Bernstein IL (1999) Insular cortex lesions and taste aversion learning: effects of conditioning method and timing of lesion. Brain Res 839:323–330

    Article  PubMed  CAS  Google Scholar 

  • Dantzer R, Konsman JP, Bluthe RM, Kelley KW (2000) Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent? Auton Neurosci 85:60–65

    Article  PubMed  CAS  Google Scholar 

  • 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 9:46–56

    Article  PubMed  CAS  Google Scholar 

  • Doenlen R, Krügel U, Wirth T, Riether C, Engler A, Prager G, Engler H, Schedlowski M, Pacheco-López G (2011) Electrical activity in rat cortico-limbic structures after single or repeated administration of lipopolysaccharide or staphylococcal enterotoxin B. Proc Biol Sci 278:1864–1872

    Article  PubMed  CAS  Google Scholar 

  • Doering B, Rief W (2012) Utilizing placebo mechanisms for dose reduction in pharmaco-therapy. Trends Pharmacol Sci 33:165–172

    Article  PubMed  CAS  Google Scholar 

  • Dudai Y, Eisenberg M (2004) Rites of passage of the Engram: reconsolidation and the lingering consolidation hypothesis. Neuron 44:93–100

    Article  PubMed  CAS  Google Scholar 

  • Eisenberg M, Kobilo T, Berman DE, Dudai Y (2003) Stability of retrieved memory: inverse correlation with trace dominance. Science 301:1102–1104

    Article  PubMed  CAS  Google Scholar 

  • Enck P, Benedetti F, Schedlowski M (2008) New insights into the placebo and nocebo responses. Neuron 59:195–206

    Article  PubMed  CAS  Google Scholar 

  • Exton MS, von Horsten S, Schult M, Voge J, Strubel T, Donath S, Steinmuller C, Seeliger H, Nagel E, Westermann J, Schedlowski M (1998) Behaviorally conditioned immunosuppression using cyclosporine A: central nervous system reduces IL-2 production via splenic innervation. J Neuroimmunol 88:182–191

    Article  PubMed  CAS  Google Scholar 

  • Exton MS, Schult M, Donath S, Strubel T, Bode U, del Rey A, Westermann J, Schedlowski M (1999) Conditioned immunosuppression makes subtherapeutic cyclosporin effective via splenic innervation. Am J Physiol 276:1710–1717

    Google Scholar 

  • Exton MS, Elfers A, Jeong WY, Bull DF, Westermann J, Schedlowski M (2000a) Conditioned suppression of contact sensitivity is independent of sympathetic splenic innervation. Am J Physiol Regul Integr Comp Physiol 279:1310–1315

    Google Scholar 

  • Exton MS, von Horsten S, Strubel T, Donath S, Schedlowski M, Westermann J (2000b) Conditioned alterations of specific blood leukocyte subsets are reconditionable. Neuroimmunomodulation 7:106–114

    Article  PubMed  CAS  Google Scholar 

  • Exton MS, Herklotz J, Westermann J, Schedlowski M (2001) Conditioning in the rat: an in vivo model to investigate the molecular mechanisms and clinical implications of brain-immune communication. Immunol Rev 184:226–235

    Article  PubMed  CAS  Google Scholar 

  • Exton MS, Gierse C, Meier B, Mosen M, Xie Y, Frede S, Goebel MU, Limmroth V, Schedlowski M (2002) Behaviorally conditioned immunosuppression in the rat is regulated via noradrenaline and beta-adrenoceptors. J Neuroimmunol 131:21–30

    Article  PubMed  CAS  Google Scholar 

  • Felten SY, Olschowka J (1987) Noradrenergic sympathetic innervation of the spleen: II. Tyrosine hydroxylase (TH)-positive nerve terminals form synapticlike contacts on lymphocytes in the splenic white pulp. J Neurosci Res 18:37–48

    Article  PubMed  CAS  Google Scholar 

  • Garcia J, Kimeldorf DJ, Koelling RA (1955) Conditioned aversion to saccharin resulting from exposure to gamma radiation. Science 122:157–158

    PubMed  CAS  Google Scholar 

  • Garcia J, Lasiter PS, Bermudez-Rattoni F, Deems DA (1985) A general theory of aversion learning. Ann N Y Acad Sci 443:8–21

    Article  PubMed  CAS  Google Scholar 

  • Garcia-DeLaTorre P, Rodriguez-Ortiz CJ, Arreguin-Martinez JL, Cruz-Castaneda P, Bermudez-Rattoni F (2009) Simultaneous but not independent anisomycin infusions in insular cortex and amygdala hinder stabilization of taste memory when updated. Learn Mem 16:514–519

    Article  PubMed  Google Scholar 

  • Garg SK, Banerjee R, Kipnis J (2008) Neuroprotective immunity: T cell-derived glutamate endows astrocytes with a neuroprotective phenotype. J Immunol 180:3866–3873

    PubMed  CAS  Google Scholar 

  • Gauci M, Husband AJ, Saxarra H, King MG (1994) Pavlovian conditioning of nasal tryptase release in human subjects with allergic rhinitis. Physiol Behav 55:823–825

    Article  PubMed  CAS  Google Scholar 

  • Giang DW, Goodman AD, Schiffer RB, Mattson DH, Petrie M, Cohen N, Ader R (1996) Conditioning of cyclophosphamide-induced leukopenia in humans. J Neuropsychiatry Clin Neurosci 8:194–201

    PubMed  CAS  Google Scholar 

  • Goebel MU, Trebst AE, Steiner J, Xie YF, Exton MS, Frede S, Canbay AE, Michel MC, Heemann U, Schedlowski M (2002) Behavioral conditioning of immunosuppression is possible in humans. FASEB J 16:1869–1873

    Article  PubMed  CAS  Google Scholar 

  • Goebel MU, Meykadeh N, Kou W, Schedlowski M, Hengge UR (2008) Behavioral conditioning of antihistamine effects in patients with allergic rhinitis. Psychother Psychosom 77:227–234

    Article  PubMed  Google Scholar 

  • Goehler LE, Gaykema RP, Hansen MK, Anderson K, Maier SF, Watkins LR (2000) Vagal immune-to-brain communication: a visceral chemosensory pathway. Auton Neurosci 85:49–59

    Article  PubMed  CAS  Google Scholar 

  • Goehler LE, Erisir A, Gaykema RP (2006) Neural–immune interface in the rat area postrema. Neuroscience 140:1415–1434

    Article  PubMed  CAS  Google Scholar 

  • Goehler LE, Lyte M, Gaykema RP (2007) Infection-induced viscerosensory signals from the gut enhance anxiety: implications for psychoneuroimmunology. Brain Behav Immun 21:721–726

    Article  PubMed  CAS  Google Scholar 

  • Gottschalk S, Cummins CL, Leibfritz D, Christians U et al (2010) Age and sex differences in the effects of the immunosuppressants cyclosporine, sirolimus and everolimus on rat brain metabolism. Neurotoxicology 32:50–57

    Article  PubMed  Google Scholar 

  • Halloran PF, Helms LM, Kung L, Noujaim J (1999) The temporal profile of calcineurin inhibition by cyclosporine in vivo. Transplantation 68:1356–1361

    Article  PubMed  CAS  Google Scholar 

  • Hansen MK, Daniels S, Goehler LE, Gaykema RP, Maier SF, Watkins LR (2000) Subdiaphragmatic vagotomy does not block intraperitoneal lipopolysaccharide-induced fever. Auton Neurosci 85:83–87

    Article  PubMed  CAS  Google Scholar 

  • Hiramoto R, Hiramoto N, Rish M, Soong S, Miller D, Ghanta V (1991) Role of immune cells in the Pavlovian conditioning of specific resistance to cancer. Int J Neurosci 59:101–117

    Article  PubMed  CAS  Google Scholar 

  • Kapturczak MH, Meier-Kriesche HU, Kaplan B (2004) Pharmacology of calcineurin antagonists. Transplant Proc 36:25–32

    Article  Google Scholar 

  • Klosterhalfen W, Klosterhalfen S (1983) Pavlovian conditioning of immunosuppression modifies adjuvant arthritis in rats. Behav Neurosci 97:663–666

    Article  PubMed  CAS  Google Scholar 

  • Klosterhalfen S, Klosterhalfen W (1990) Conditioned cyclosporine effects but not conditioned taste aversion in immunized rats. Behav Neurosci 104:716–724

    Article  PubMed  CAS  Google Scholar 

  • Leech J, Mazzone SB, Farrell MJ (2012) The effect of placebo conditioning on capsaicin-evoked urge-to-cough. Chest. doi:10.1378

  • Longo DL, Duffey PL, Kopp WC, Heyes MP, Alvord WG, Sharfman WH, Schmidt PJ, Rubinow DR, Rosenstein D (1999) Conditioned immune response to interferon-gamma in humans. Clin Immunol 90:173–181

    Article  PubMed  CAS  Google Scholar 

  • Lyson T, McMullan DM, Ermel LD, Morgan BJ, Victor RG (1994) Mechanism of cyclosporine-induced sympathetic activation and acute hypertension in rats. Hypertension 23:667–675

    Article  PubMed  CAS  Google Scholar 

  • Maier SF, Goehler LE, Fleshner M, Watkins LR (1998) The role of the vagus nerve in cytokine-to-brain communication. Ann N Y Acad Sci 840:289–300

    Article  PubMed  CAS  Google Scholar 

  • McCaffrey PG, Luo C, Kerppola TK, Jain J, Badalian TM, Ho AM, Burgeon E, Lane WS, Lambert JN, Curran T (1993) Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science 262:750–754

    Article  PubMed  CAS  Google Scholar 

  • Monfils MH, Cowansage KK, Klann E, LeDoux JE (2009) Extinction-reconsolidation boundaries: key to persistent attenuation of fear memories. Science 324:951–955

    Article  PubMed  CAS  Google Scholar 

  • Moss NG, Powell SL, Falk RJ (1985) Intravenous cyclosporine activates afferent and efferent renal nerves and causes sodium retention in innervated kidneys in rats. Proc Natl Acad Sci U S A 82:8222–8226

    Article  PubMed  CAS  Google Scholar 

  • Myers KM, Carlezon WA Jr (2010) Extinction of drug- and withdrawal-paired cues in animal models: relevance to the treatment of addiction. Neurosci Biobehav Rev 35:285–302

    Article  PubMed  Google Scholar 

  • Nader K, Hardt O (2009) A single standard for memory: the case for reconsolidation. Nat Rev Neurosci 10:224–234

    Article  PubMed  CAS  Google Scholar 

  • Nance DM, Sanders VM (2007) Autonomic innervation and regulation of the immune system (1987–2007). Brain Behav Immun 21:736–745

    Article  PubMed  CAS  Google Scholar 

  • Ober K, Benson S, Vogelsang M, Bylica A, Günther D, Witzke O, Kribben A, Engler H, Schedlowski M (2012) Plasma noradrenaline and state anxiety levels predict placebo response in learned immunosuppression. Clin Pharmacol Ther 91:220–226

    Article  PubMed  CAS  Google Scholar 

  • Pacheco-López G, Bermúdez-Rattoni F (2011) Brain-immune interactions and the neural basis of disease-avoidant ingestive behaviour. Philos Trans R Soc Lond B Biol Sci 366:3389–3405

    Article  PubMed  Google Scholar 

  • Pacheco-López G, Niemi MB, Kou W, Härting M, Fandrey J, Schedlowski M (2005) Neural substrates for behaviorally conditioned immunosuppression in the rat. J Neurosci 25:2330–2337

    Article  PubMed  Google Scholar 

  • Pacheco-López G, Engler H, Niemi MB, Schedlowski M (2006) Expectations and associations that heal: immunomodulatory placebo effects and its neurobiology. Brain Behav Immun 20:430–446

    Article  PubMed  Google Scholar 

  • Pacheco-López G, Riether C, Doenlen R, Engler H, Niemi MB, Engler A, Kavelaars A, Heijnen CJ, Schedlowski M (2009) Calcineurin inhibition in splenocytes induced by pavlovian conditioning. FASEB J 23:1161–1167

    Article  PubMed  Google Scholar 

  • Pacheco-López G, Doenlen R, Krügel U, Arnold M, Wirth T, Riether C, Engler A, Niemi MB, Christians U, Engler H, Schedlowski M (2012) Neurobehavioural activation during peripheral immunosuppression. Int J Neuropsychopharmacol 5:1–13

    Google Scholar 

  • Pavlov I (1927) Conditioned reflexes: an investigation of the physiological activity of the cerebral cortex. Oxford University Press, Cambridge

    Google Scholar 

  • Ramírez-Amaya V, Bermúdez-Rattoni F (1999) Conditioned enhancement of antibody production is disrupted by insular cortex and amygdala but not hippocampal lesions. Brain Behav Immun 13:46–60

    Article  PubMed  Google Scholar 

  • Rief W, Bingel U, Schedlowski M, Enck P (2011) Mechanisms involved in placebo and nocebo responses and implications for drug trials. Clin Pharmacol Ther 90:722–726

    Article  PubMed  CAS  Google Scholar 

  • Riether C, Doenlen R, Pacheco-Lopez G, Niemi MB, Engler A, Engler H, Schedlowski M (2008) Behavioural conditioning of immune functions: how the central nervous system controls peripheral immune responses by evoking associative learning processes. Rev Neurosci 19:1–17

    Article  PubMed  Google Scholar 

  • Riether C, Kavelaars A, Wirth T, Pacheco-López G, Doenlen R, Willemen H, Cj Heijnen, Schedlowski M, Engler H (2011) Stimulation of β2-adrenergic receptors inhibits calcineurin activity in CD4+ T cells via PKA-AKAP interaction. Brain Behav Immun 25:59–66

    Article  PubMed  CAS  Google Scholar 

  • Romanovsky AA (2000) Thermoregulatory manifestations of systemic inflammation: lessons from vagotomy. Auton Neurosci 85:39–48

    Article  PubMed  CAS  Google Scholar 

  • Romanovsky AA, Simons CT, Szekely M, Kulchitsky VA (1997) The vagus nerve in the thermoregulatory response to systemic inflammation. Am J Physiol 273:407–413

    Google Scholar 

  • Romanovsky AA, Ivanov AI, Lenczowski MJ, Kulchitsky VA, Van Dam AM, Poole S, Homer LD, Tilders FJ (2000) Lipopolysaccharide transport from the peritoneal cavity to the blood: is it controlled by the vagus nerve? Auton Neurosci 85:133–140

    Article  PubMed  CAS  Google Scholar 

  • Rosas JM, Bouton ME (1997) Renewal of a conditioned taste aversion upon return to the conditioning context after extinction in another one. Learn Motiv 28:216–229

    Article  Google Scholar 

  • Rosas JM, Bouton ME (1998) Context change and retention interval can have additive, rather than interactive, effects after taste aversion extinction. Psychon Bull Rev 5:79–83

    Article  Google Scholar 

  • Sanders V, Kohm A (2002) Sympathetic nervous system interaction with the immune system. Int Rev Neurobiol 52:17–41

    Article  PubMed  CAS  Google Scholar 

  • Sanders VM, Straub RH (2002) Norepinephrine, the beta-adrenergic receptor, and immunity. Brain Behav Immun 16:290–332

    Article  PubMed  CAS  Google Scholar 

  • Sandler AD, Glesne CE, Bodfish JW (2010) Conditioned placebo dose reduction: a new treatment in attention-deficit hyperactivity disorder? J Dev Behav Pediatr 31:369–375

    Article  PubMed  Google Scholar 

  • Sato Y, Takayanagi Y, Onaka T, Kobayashi E (2007) Impact of cyclosporine upon emotional and social behavior in mice. Transplantation 83:1365–1370

    Article  PubMed  CAS  Google Scholar 

  • Schedlowski M, Pacheco-Lopez G (2010) The learned immune response: Pavlov and beyond. Brain Behav Immun 24:176–185

    Article  PubMed  Google Scholar 

  • Schedlowski M, Hosch W, Oberbeck R, Benschop RJ, Jacobs R, Raab HR, Schmidt RE (1996) Catecholamines modulate human NK cell circulation and function via spleen-independent beta 2-adrenergic mechanisms. J Immunol 156:93–99

    PubMed  CAS  Google Scholar 

  • Schiller D, Monfils MH, Raio CM, Johnson DC, Ledoux JE, Phelps EA (2010) Preventing the return of fear in humans using reconsolidation update mechanisms. Nature 463:49–53

    Article  PubMed  CAS  Google Scholar 

  • Sewards TV (2004) Dual separate pathways for sensory and hedonic aspects of taste. Brain Res Bull 62:271–283

    Article  PubMed  Google Scholar 

  • Sewards TV, Sewards MA (2001) Cortical association areas in the gustatory system. Neurosci Biobehav Rev 25:395–407

    Article  PubMed  CAS  Google Scholar 

  • Simon SA, de Araujo IE, Gutierrez R, Nicolelis MA (2006) The neural mechanisms of gustation: a distributed processing code. Nat Rev Neurosci 7:890–901

    Article  PubMed  CAS  Google Scholar 

  • Smith GR Jr, McDaniel SM (1983) Psychologically mediated effect on the delayed hypersensitivity reaction to tuberculin in humans. Psychosom Med 45:65–70

    PubMed  Google Scholar 

  • Spector N (1996) Neuroimmunomodulation: a brief review. Can conditioning of natural killer cell activity reverse cancer and/or aging? Regul Toxicol Pharmacol 24:32–38

    Article  Google Scholar 

  • Steinbach WJ, Reedy JL, Cramer RA, Perfect JR, Heitma J (2007) Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. Nat Rev Microbiology 5:418–430

    Article  CAS  Google Scholar 

  • Tracey KJ (2010) Understanding immunity requires more than immunology. Nat Immunol 11:561–564

    Article  PubMed  CAS  Google Scholar 

  • Tronson NC, Taylor JR (2007) Molecular mechanisms of memory reconsolidation. Nat Rev Neurosci 8:262–275

    Article  PubMed  CAS  Google Scholar 

  • von Horsten S, Exton MS, Voge J, Schult M et al (1998) Cyclosporine A affects open field behavior in DA rats. Pharmacol Biochem Behav 60:71–76

    Article  Google Scholar 

  • Welzl H, D’Adamo P, Lipp HP (2001) Conditioned taste aversion as a learning and memory paradigm. Behav Brain Res 125:205–213

    Article  PubMed  CAS  Google Scholar 

  • Wirth T, Ober K, Prager G, Vogelsang M, Benson S, Witzke O, Kribben A, Engler H, Schedlowski M (2011) Repeated recall of learned immunosuppression: evidence from rats and men. Brain Behav Immun 25:1444–1451

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto T, Shimura T, Sako N, Yasoshima Y, Sakai N (1994) Neural substrates for conditioned taste aversion in the rat. Behav Brain Res 65:123–137

    Article  PubMed  CAS  Google Scholar 

  • Zhang W, Li JL, Hosaka M, Janz R et al (2000) Cyclosporine A-induced hypertension involves synapsin in renal sensory nerve endings. Proc Natl Acad Sci U S A 97:9765–9770

    Article  PubMed  CAS  Google Scholar 

  • Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, Cohen H, Kipnis J, Schwartz M (2006) Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci 9:268–275

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by a grant of the German Research Foundation (DFG) (Sche 341/19-1).

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  1. Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany

    Martin Hadamitzky, Harald Engler & Manfred Schedlowski

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  1. Martin Hadamitzky
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Correspondence to Martin Hadamitzky.

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Hadamitzky, M., Engler, H. & Schedlowski, M. Learned Immunosuppression: Extinction, Renewal, and the Challenge of Reconsolidation. J Neuroimmune Pharmacol 8, 180–188 (2013). https://doi.org/10.1007/s11481-012-9388-6

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