IMMUNE DYSFUNCTION АND COGNITIVE DEFICIT IN STRESS AND PHYSIOLOGICAL AGING (PART I): PATHOGENESIS AND RISK FACTORS

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Abstract

The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets.
The brain, immune and endocrine systems being the principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain cells secluded from the blood flow by a specialized blood-brain-barrier (BBB) can endogenously express pro- and anti-inflammatory cytokines without
the intervention of the immune system. In normal brain the cytokine signaling rather contributes to exclusive brain function (e.g. long-term
potentiation, synaptic plasticity, adult neurogenesis) than serves as immune communicator. The stress of different origin increases the serum
cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Mass intrusion
of biologically active peptides having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments.
In addition owing to BBB disruption dendritic cells and T cells also penetrate into the brain where they take up a perivascular position. The changes observed in stressed subject may accumulate during repeated episodes of stress forming a picture typical of the aging brain. Moreover long-term stress as well as physiological aging result in hormonal and immunological disturbances including hypothalamic-pituitary-adrenal axis depletion, regulatory T-cell accumulation and dehydroepiandrosterone decrease.

About the authors

A. L. Pukhal'skii

Research Centre for Medical Genetics, Moscow, Russian Federation

Email: osugariver@yahoo.com

PhD, professor, chief research scientist of the Department of Cystic Fibrosis of Research Centre of Medical Genetics (RCMG). Address: 1, Moskvorech’e Street, Moscow, RF, 115478.

Russian Federation

G. V. Shmarina

Research Centre for Medical Genetics, Moscow

Author for correspondence.
Email: osugariver@yahoo.com
MD, leading research scientist of the Department of Cystic Fibrosis of Research Centre of Medical Genetics (RCMG) Russian Federation

V. A. Aleshkin

Gabrichevsky Institute of Epidemiology and Microbiology, Moscow

Email: info@gabrich.com
PhD, professor, Director of G.N.Gabrichevskii Moscow Research Institute of Epidemiology and Microbiology Russian Federation

References

  1. Maninger N., Wolokowitz O.M., Reus V.I. et al. Neurological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Front. Neuroendocrinoil. 2009;
  2. : 65–91.
  3. Hazeldine J., Arlt W., Lord J.M. Dehydroepiandrosterone
  4. as a regulator of immune cell function. J. Steroid Biochem. Mol. Biol. 2010; 120: 127–136.
  5. Goncharov N.P., Katsiya G.V. V kn.: Gormon zdorov'ya i dolgoletiya [In book Hormone of Health and Longevity]. Moscow, ADAMANT", 2012. 159 p.
  6. Chen J., Johnson R.W. Dehydroepiandrosterone-sulfate did not mitigate sickness behavior in mice. Physiol. Behav. 2004; 82: 713–719.
  7. Labrie F., Belanger A., Cusan L. et al. Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. J. Clin. Endocrinol. Metab. 1997; 82: 2396–2402.
  8. Sulcova J., Hill M., Hampl R., Starka L. Age and sex related differences in serum levels of unconjugated dehydroepiandrosterone and its sulphate in normal subjects. J. Endocrinol. 1997; 154: 57–62.
  9. Pukhalsky A., Shmarina G., Alioshkin V. The Number of
  10. Regulatory T Cells : Purs uit of the Golden Mean. In: Regulatory T Cells. R.S. Hayashi (ed.). Nova Science Publishers Inc. 2010. P. 261–268.
  11. Pukhal'skii A.L., Shmarina G.V., Aleshkin V.A. Vestnik RAMN = Annals of RAMS. 2011; 8: 24–33.
  12. Elenkov I.J., Iezzoni D.G., Daly A. et al. Cytokine disregulation, inflammation and well-being. Neuroimmunomodulation. 2005; 12: 255–269.
  13. Dhabhar F.S, Malarkey W.B., Neri E., McEwen B.S. Stress-induced redistribution of immune cells — from barracks to boulevards to battlefields: a tale of three hormones — Curt Richter Award winner. Psychoneuroendocrinology. 2012; 37: 1345–1368.
  14. Ziv Y., Ron N., Butovsky O. et al. Immunecells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat. Neurosci. 2006; 9: 268–275.
  15. Wolf S.A., Steiner B., Akpinarli A. et al. CD4-positive T
  16. lymphocytes provide a neuroimmunological link in the control of adult hippocampal neurogenesis. J. Immunol. 2009; 182: 3979–3984.
  17. Wolf S.A., Steiner B., Wengner A. et al. Adaptive peripheral immune response increases proliferation of neural precursor cells in the adult hippocampus. FASEB J. 2009; 23: 3121–3128.
  18. Ron-Harel N., Cardon M., Schwartz M. Brain homeostasis is maintained by «danger» signals stimulating a supportive immune response within the brain’s borders. Brain Behav. Immun. 2011; 25: 1036–1043.
  19. Sorrells S.F., Caso J.R., Munhoz C.D., Sapolsky R.M. The stressed CNS: when glucocorticoids aggravate inflammation. Neuron. 2009; 64: 33–39.
  20. Yirmiya R., Goshen I. Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav. Immun. 2011; 25: 181–213.
  21. Yuen E.Y., Liu W., Karatsoreos I.N. et al. Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory. Proc. Natl. Acad. Sci. USA. 2009; 106: 14075–14079.
  22. Garcia-Bueno B., Caso J.R., Leza J.C. Stress as a neuroinflammatory condition in brain: damaging and protective mechanisms. Neurosci. Biobehav. Rev. 2008; 32: 1136–1151.
  23. Mathieu P., Battista D., Depino A. et al. The more you
  24. have, the less you get: the functional role of inflammation on neuronal differentiation of endogenous and transplanted neural stem cells in the adult brain. J. Neurochem. 2010; 112: 1368–1385.
  25. Finch C.E., Laping N.J., Morgan T.E. et al. TGF-beta 1 is an organizer of responses to neurodegeneration. J. Cell Biochem. 1993; 53: 314–322.
  26. Nolan Y., Maher F.O., Martin D.S. et al. Role of interleukin-4 in regulation of age-related inflammatory changes in the hippocampus. Biol. Chem. 2005; 280: 9354–9362.
  27. Negrini S., Fenoglio D., Balestra P. et al. Endocrine regulation of suppressor lymphocytes. Role of the glucocorticoids-induced TNF-like receptor. Ann. NY Acad. Sci. 2006; 1069: 377–385.
  28. Wilkinson C.W., Petrie E.C., Murray S.R. et al. Human
  29. glucocorticoid feedback inhibition is reduced in older individuals: evening study. J. Clin. Endocrinol. Metab. 2001; 86: 545–550.
  30. Heffner K.L. Neuroendocrine effects of stress on immunity in the elderly: implications for inflammatory disease. Immunol. Allergy Clin. North Am. 2011; 31: 95–108.
  31. Bornstein S.R., Engeland W.C., Ehrhart-Bornstein M., Herman J.P. Dissociation of ACTH and glucocorticoids. Trends Endocrinol. Metab. 2008; 19 (5): 175–180.
  32. Butcher S.K., Lord J.M. Stress responses and innate immunity: aging as a contributory factor. Aging Cell. 2004; 3: 151–160.
  33. Godbout J.P., Moreau M., Lestage J. et al. Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system. Neuropsychopharmacology. 2008; 33: 2341–2351.
  34. Buchanan J.B., Sparkman N.L., Chen J., Johnson R.W. Cognitive and neuroinflammatory consequences of mild repeated stress are exacerbated in aged mice. Psychoneuroendocrinology. 2008; 33: 755–765.
  35. Bower J.E., Ganz P.A., Aziz N. Altered cortisol response to psychologic stress in breast cancer survivors with persistent fatigue. Psychosom. Med. 2005; 67: 277–280.
  36. Gaab, J., Baumann S., Budnoik A. et al. Reduced reactivity and enhanced negative feedback sensitivity of the hypothalamuspituitary- adrenal axis in chronic whiplash-associated disorder. Pain. 2005; 119: 219–224.
  37. Weiner H.L. Induction and mechanism of action of transforming growth factor-β-secreting Th3 regulatory cells. Immunol. Rev. 2001; 182: 207–214.
  38. Kipnis J., Schwartz M. Controlled autoimmunity in CNS
  39. maintenance and repair: naturally occurring CD4+CD25+
  40. regulatory T-Cells at the crossroads of health and disease.
  41. Neuromolecular. Med. 2005; 7: 197–206.
  42. Cohen H., Ziv Y., Cardon M. et al. Maladaptation to mental stress mitigated by the adaptive immune system via depletion of naturally occurring regulatory CD4+CD25+ cells. J. Neurobiol. 2006; 66: 552–563.
  43. Pukhalsky A.L., Shmarina G.V., Alioshkin V.A., Sabelnikov A. HPA axis exhaustion and regulatory T cell accumulation in patients with a functional somatic syndrome: recent view on the problem of Gulf War veterans. J. Neuroimmunol. 2008; 196 (1–2): 133–138.
  44. Wekerle H., Sun D.M. Fragile privileges: autoimmunity in brain and eye. Acta Pharmacol. Sin. 2010; 31: 1141–1148.
  45. Neumann H., Boucraut J., Hahnel C. et al. Neuronal control of MHC class II inducibility in rat astrocytes and microglia. Eur. J. Neurosci. 1996; 8: 2582–2590.
  46. Neumann H., Misgeld T., Matsumuro K., Wekerle H. Neurotrophins inhibit major histocompatibility class II inducibility of microglia: involvement of the p75 neurotrophin receptor. Proc. Natl. Acad. Sci. USA. 1998; 95: 5779–5784.
  47. Spalding K.L., Bergmann O., Alkass K. et al. Dynamics of hippocampal neurogenesis in adult humans. Cell. 2013; 153 (6): 1219–1227.
  48. Ziv Y., Schwartz M. Immune-based regulation of adult neurogenesis: implications for learning and memory. Brain Behav. Immun. 2008; 22: 167–176.
  49. Pette M., Fujita K., Kitze B. et al. Myelin basic protein-specific T lymphocyte lines from MS patients and healthy individuals. Neurology. 1990; 40: 1770–1776.
  50. Loewenbrueck K.F., Tigno-Aranjuez J.T., Boehm B.O. et al. Th1 responses to beta-amyloid in young humans convert to regulatory IL-10 responses in Down syndrome and Alzheimer’s disease. Neurobiol. Aging. 2010; 31: 1732–1742.
  51. Derecki N.C., Privman E., Kipnis J. Rett syndrome and other autism spectrum disorders--brain diseases of immune malfunction? Mol. Psychiatry. 2010; 15: 355–363.
  52. Palumbo M.L., Canzobre M.C., Pascuan C.G. et al. Stress induced cognitive deficit is differentially modulated in BALB/c and C57Bl/6 mice: correlation with Th1/Th2 balance after stress exposure. Neuroimmunology. 2010; 218: 12–20.
  53. Miyazaki T., Ishikawa T., Nakata A. et al. Association between perceived social support and Th1 dominance. Biol. Psychol. 2005; 70: 30–37.
  54. Suzuki T., Suzuki N., Engleman E.G. et al. Low serum levels of dehydroepiandrosterone may cause deficient IL-2 production by lymphocytes in patients with systemic lupus erythematosus (SLE). Clin. Exp. Immunol. 1995; 99: 251–255.
  55. Setoguchi R., Hori,S., Takahashi T., Sakaguchi S. Homeostatic maintenance of natural Foxp3+ CD25+ CD4+ regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J. Exp. Med. 2005; 201: 723–735.
  56. Darrasse-Jeze G., Deroubaix S., Mouquet H. et al. Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. J. Exp. Med. 2009; 206: 1853–1862.
  57. Tesar B.M., Du W., Shirali A.C., Walker W.E. et al. Aging augments IL-17 T-cell alloimmune responses. Am. J. Transplant. 2008; 9: 54–63.
  58. Wuest T.Y., Willette-Brown J., Durum S.K., Hurwitz A.A. The influence of IL-2 family cytokines on activation and function of naturally occurring regulatory T cells. J. Leukoc. Biol. 2008; 84: 973–980.
  59. Godbout J.P., Moreau M., Lestage J. Aging exacerbates depressivelike behavior in mice in response to activation of the peripheral innate immune system. Neuropsychopharmacology. 2008; 33: 2341–2351.
  60. Mooradian A.D. Effect of aging on the blood-brain barrier. Neurobiol Aging. 1988; 9: 31–39.
  61. Morita T., Mizutani Y., Sawada M., Shimada A. Immunohistochemical and ultrastructural findings related to the blood--brain barrier in the blood vessels of the cerebral white matter in aged dogs. J. Comp. Pathol. 2005; 133: 14–22.
  62. Stichel C.C., Luebbert H. Inflammatory processes in the aging mouse brain: participation of dendritic cells and T-cells. Neurobiol. Aging. 2007; 28: 1507–1521.
  63. Kaunzner U.W., Miller M.M., Gottfried-Blackmore A. et al. Accumulation of resident and peripheral dendritic cells in the aging CNS. Neurobiol. Aging. 2012; 33: 681–693.
  64. Pukhalsky A.L., Toptygina A.P. Genetic control of interleukin-2 production in inbred mice. Biull. Eksp. Biol. Med. 1989; 108 (9): 311–313.
  65. Yates J., Rovis F., Mitchell P. et al. The maintenance human CD4+CD25+ regulatory T cell function: IL-2, IL-4, IL-7 and IL-15 preserve optimal suppressive potency in vitro. Int. Immunol. 2007; 19: 785–799.
  66. Passerini L., Allan S.E., Battaglia M. et al. STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+. Int. Immunol. 2008; 20: 421–
  67. Cohen A.C., Nadeau K.C., Tu W. et al. Cutting edge: decreased accumulation and regulatory function of CD4+ CD25(high) T cells in human STAT5b deficiency. J. Immunol. 2006; 177: 2770– 2774.
  68. Chen X., Oppenheim J.J., Howard O.M. BALB/c mice have more CD4+CD25+ T regulatory cells and show greater susceptibility to suppression of their CD4+CD25- responder T cells than C57BL/6 mice. J. Leukoc. Biol. 2005; 78: 114–121.
  69. Roque S., Nobrega C., Appelberg R., Correia-Neves M. IL-10 underlies distinct susceptibility of BALB/c and C57BL/6 mice to Mycobacterium avium infection and influences efficacy of antibiotic therapy. J. Immunol. 2007; 178: 8028–8035.
  70. Pukhalsky A., Shmarina G., Alioshkin V. The Number of Regulatory T Cells: Pursuit of the Golden Mean. In: Regulatory T Cells. Ren S. Hayashi (ed.). New York, Nova Science Publishers Inc., 2010. pp. 261–268.
  71. Tagawa N., Sugimoto Y., Yamada J., Kobayashi Y. Strain differences of neurosteroid levels in mouse brain. Steroids. 2006; 71: 776– 784.
  72. Xie T., Rowen L., Aguado B. et al. Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse. Genome Res. 2003; 13: 2621–2636.
  73. Locksley R.M., Killeen N., Lenardo M.J. The TNF and TNF
  74. receptor superfamilies: integrating mammalian biology. Cell. 2001; 104: 487–501.
  75. Elewaut D., Ware C.F. The unconventional role of LT alpha beta in T cell differentiation. Trends Immunol 2007; 28: 169–175.
  76. Beste C., Baune B.T., Falkenstein M., Konrad C. Variations in the TNF-α gene (TNF-α -308G→A) affect attention and action selection mechanisms in a dissociated fashion. J. Neurophysiol. 2010; 104: 2523–2531.
  77. Beste C., Gunturkun O., Baune B.T. et al. Double dissociated effects of the functional TNF-α -308G/A polymorphism on processes of cognitive control. Neuropsychologia. 2011; 49: 196–202.
  78. Pukhalsky A.L., Shmarina G.V., Kapustin I.V. et al. Genetic heterogeneity of heat shock protein synthesis as a factor determining the resistance to stressors in mammalia. Cell & Tissue Biol. 2011; 5 (1): 22–28.
  79. Pukhalsky A.L., Toptygina A.P., Viktorov V.V. Pharmacokinetics of alkylating metabolites of cyclophosphamide in different strains of mice. Int. J. Immunopharmacol. 1990; 12: 217–223.
  80. Zhang X., Beaulieu J.M., Sotnikova T.D. et al. Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science. 2004; 305: 217.

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