Skip to main content
Log in

Neurochemistry of Brain Neuroendocrine Immune System: Signal Molecules

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The aim of this review is not so much to show the problem of neuroendocrine, neurophysiologic, and neurochemical mechanisms of the immune system regulation of the organism by brain (there is a great deal of literature about it), as to solve the problem of whether the brain itself is an immune organ, and also to define cellular, neurochemical, and immunological properties of the brain for its immune defense when the blood-brain barrier is not damaged in spite of the penetration of the infection to brain. The accumulated literary data on CNS interaction with the immune system, expression of several cytokines and their receptors in the neurons of human brain culture, in astrocytes and microglia, all testify to the existence of a brain immune system. Recently studies appeared on the expression of major histocompatibility complex in brain neurons. It does not exclude the possibility of expression of immunoglobulins (or immunoglobulin-like proteins) in brain cells. Data obtained by us on the biosynthesis of a number of known interleukins and new cytokines in neurosecretory neurons of hypothalamus (N.Paraventricularis and N.Supraopticus) demonstrate that neuroendocrine nuclei of the hypothalamus are the center for neuroendocrine and immune systems of brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Brightman, M. W., Ishihara, S., and Chang, L. 1995. Penetration of solutes, viruses and cells across the blood-brain barrier. Curr. Top. Microbiol. Immunol. 202:63-78.

    Google Scholar 

  2. Kreutzberg, G. W. 1996. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 19:312-318.

    Google Scholar 

  3. Fleshner, M., Goehler, L. E., Hermann, J., Relton, J. K., Maier, S. F., and Watkin, L. R. 1995. Interleukin-lβinduced corticosterone elevation and hypothalamic NE depletion is vagally mediated. Brain Res. Bull. 37:605-610.

    Google Scholar 

  4. Laye, S., Bluthe, R. M., Kent, S., Lombe, C., Medina, C., Parnet, P., Kelley, K., and Dantrer, R. 1995. Subdiaphragmatic vagotomy blocks induction of IL-1βmRNA in mice brain in response to peripheral LPS. Am. J. Physiol. 268(Pt2):R1327-331.

    Google Scholar 

  5. Saphir, D., Abramsky, O., Mor, G., and Ovadia, H. 1987. Multiunit electrical activity in conscious rats during on immune response. Brain Behav. Immunol. 1:40-51.

    Google Scholar 

  6. Besedovsky, H. O., del Rey, A., Da Prada, M., and Keller, H. H. 1979. Immunoregulation mediated by the sympathetic nervous system. Cell. Immunol. 48:346-355.

    Google Scholar 

  7. Dunn, A. A., Powell, M. L., Meitin, C., and Small, Jr., P. A. 1989. Virus infection as a stressor, influenza virus elevates plasma corticosterone and brain concentration of MHPG and tryptophan. Physiol. Behav. 45:591-594.

    Google Scholar 

  8. Rebar, R. W., Miyake, A., Low, T. L. K., and Goldstein, A. L. 1981. Thymosin stimualates secretion of Luteinizing hormone-releasing factor. Science 214:669-671.

    Google Scholar 

  9. Galoyan, A. A., Chailian, S. G., and Abrahamian, G. E. 1992. The role of Tβ1 in the regulation of Ca2+and calmodulin-sensitive processes (regulation of PDE activity). Neurochem. (USSR). 11:10-20.

    Google Scholar 

  10. Azakawa, H., Nagase, H., Hayashi, N., Fujwara, T., Ogawa, M., Shin, S., and Nakumura, Y. 1994. BBRG. 200:836-843.

    Google Scholar 

  11. Galoyan, A. A., Gurvits, B. Ya., Shuvalova, L. A., Davis, M. T., Shively, J. E., and Lee, T. D. 1992. A hypothalamic activator of calmodulin-dependent enzymes is thymosin β4 (1-39). Neurochem. Res. 17:773-777.

    Google Scholar 

  12. Voelter, W., Kapurniotu, A., Mihelic, M., Gurvits, B. Ya., Abrahamian, G. E., and Galoyan, A. A. 1995. The interaction of (1-4) fragment of Tβ4 with calmodulin-sensitive cAMP PDE from hypothalamus. Neurochem. Res. 20:55-59.

    Google Scholar 

  13. Galoyan, A. A. 1997. Biochemistry of Novel Cardioactive Hormones and Immunomodulators of the Functional System Neurosecretory Hypothalamus-Endocrine Heart. Nauka publishers, Moscow, Pages-240.

    Google Scholar 

  14. Galoyan, A. A. 1992. Ca-CaM replacing peptide systems of hypothalamus new level of CaM-activated enzymes regulation. Dokl. Akad. Nauk RA, 92:173-176.

    Google Scholar 

  15. Galoyan, A. A., Gurvits, B. Ya., and Sharova, N. P. 1989. Cyclic nucleotide PDE and 5'-nucleotidase: a coupled system. Neurochem. Res. 14:1213-1221.

    Google Scholar 

  16. Galoyan, A. A. and Gurvits, B. Y. 1992. The discovery of peptidyl-prolyl-cis trans isomerase in hypothalamus (its new functions). Neurochem. (USSR). 11:89-92.

    Google Scholar 

  17. Gurvits, B. Ya., Tret'akov, O. Yu., Baranova, F. S., Egorov, Ts. A., and Galoyan, A. A. 1997. On the structure and mechanisms of action of Iph-a receptor of the immunosuppressor FK506. The 2nd Meeting of the Society for Biochemistry. Moscow, Russia. Abstr. 105.

  18. Galoyan, A. A. and Gurvits, B. Ya. 1998. Brain Iphs: peptidyl-prolyl cis-trans isomerase activity, multiple forms and immunological functions. International Symposium “Protein structure, stability and folding, fundamental and medical aspects”. Moscow, Russia.

  19. Gurvits, B. Ya., Tret'akov, O. Yu., Baranova, F. S., Egorov, Ts. A., and Galoyan, A. A. 1997. On the structure and mechanisms of action of Iph-a receptor of the immunosuppressor FK506. The 2nd Meeting of the Society for Biochemistry. Moscow, Russia. Abstr. 105.

  20. Galoyan, A. A. 1998. The primary structure and biochemical mechanisms of action of newly discovered immunomodulators of brain. Abstr. of the Intern. Small Conference on “Brain and Immune System”, Yerevan-Dilidjan. Neurochem. (RAS & NAS RA). 15:82-83.

    Google Scholar 

  21. Gurvits, B. Ya., Tret'yakov, O. Yu., and Galoyan, A. A. 1998. Potentiation of FK506 action on the proliferative activity of human lymphocytes in vitro by an N-terminal peptide fragment of the 12 kd FK506-binding protein. Abstr. of the Intern. Small Conference on “Brain and Immune System”, Yerevan-Dilidjan. Neurochem. (RAS & NAS RA). 15:84-85.

    Google Scholar 

  22. Simonyan, A. A., Badalyan, R. B., Simonyan, R. A., Stepanyan, R. A., and Galoyan, A. A. 1998. Regulation of ATP-ase activity in mitochondria by 1-15 and 1-9 fragments of Iph (FK-BP). Abstr. of the Intern. Small Conference on “Brain and Immune System”, Yerevan-Dilidjan. Neurochem. (RAS & NAS RA). 15:92.

    Google Scholar 

  23. Galoyan, A. A., Sahakian, S. A., and Akopian, A. 1997. A. Immunophilin (Iph) and cardioactive neurohormones of hypothalamus in Ca2+signal transduction and control of neuronal behaviour. Joint 16-the ISN and ASN Meeting, Boston. J. Neurochem. 69(suppl.):S200 C.

    Google Scholar 

  24. Gurvits, B. Ya. and Galoyan, A. A. 1995. Structure and function of immunophilin, a receptor of immunosuppressant FK-506, isolated from bovine hypothalamus. Abstr. of the 15-th ISN Meeting, Kyoto. J. Neurochem. 65(suppl.):S178D.

    Google Scholar 

  25. Gurvits, B. Ya., Gulyaeva, N. V., and Galoyan, A. A. 1995. Peptidyl-prolyl cis-trans isomerase, thymosin and superoxide dismutase in relation to immunologic functions of the nervous system. Abstr. of the 4-the IBRO World Congress of Neuroscience, Kyoto. HA3.5. 537.

  26. Galoyan, A. A. 1995. Immunomodulators of hypothalamus: primary structure and functions. Abstract for the 3rd International Symposium on Bioorganic Chemistry. Dagomys, Russia. 6.

  27. Gurvits, B. Ya. and Galoyan, A. A. 1993. Isolation of immunophilin, a receptor of immunodepressant FK-506, for bovine hypothalamus. Abstract of the 14-the ISN Meeting, Montpellier, P.LA2-D.

  28. Karageuzyan, K. G., Galoyan, A. A., and Hovsepyan, L. M. 1998. Peculiarities of molecular mechanisms of action of the synthetic N-terminal fragments corresponding to immunophilin from bovine hypothalamus on qualitative and quantitative composition of phospholipids in rat brain slices and in erythrocyte membranes as well as on erythrocyte resistance to peroxidized hemolisis. Proceedings of the Intern. Small Conference on “Brain and Immune System”, Yerevan-Dilidjan. Neurochem. (RAS & NAS RA). 15:67-75.

    Google Scholar 

  29. Simonyan, M. A., Alexanian, R. A., Babaian, M. A., Simonian, R. M., and Galoyan, A. A. 1997. Level of endogene antioxidant and new prooxidant blood metelproteins under the influence of N-terminal (1-15) fragment of FK-BP 12 (immunophilin). Abstr. of the Intern. Small Conference on “Brain and Immune System”, Yerevan-Dilidjan. Neurochem. (RAS & NAS RA).

  30. Galoyan, A. A. 1998. Brain and Immune System (Neurochemical aspects of the problem). Proceedings of the Intern. Small Conference on “Brain and Immune System”, Yerevan-Dilidjan. Neurochem. (RAS & NAS RA). 15:3-11.

    Google Scholar 

  31. Gurvits, B. Ya., Tret'akov, O. Yu. and Galoyan, A. A. 1997. Immunologically active compounds of the brain. Neurochem. (RAS & NAS RA). 14:311-313.

    Google Scholar 

  32. Alexanian, A. R., Muradian, E. G., and Galoyan, A. A. 1998. The polyfunctional nature of Immunophilins, their role in Biochemical and Physiological Processes. Proceedings of the Intern. Small Conference on “Brain and Immune System”, Yerevan-Dilidjan. Neurochem. (RAS & NAS RA). 15:29-35.

    Google Scholar 

  33. Simonyan, M. A., Babayan, M. A., Simonyan, R. M., and Galoyan, A. A. 1998. Effects of N-terminal (1-15) Immunophilin fragment on the level of antioxidant and new pro-oxidant metaloproteins from blood. Proceedings of the Intern. Small Conference on “Brain and Immune System”, Yerevan-Dilidjan. Neurochem. (RAS & NAS RA). 15:51-55.

    Google Scholar 

  34. Sewell, T. J., Lam, E., Martin, M. M., Leszyk, J., Weider, J., Calaycay, J., Groffin, P., Williams, H., Hung S., Cryan, J., Sigal W. H., and Wiederrecht, G. J. 1994. J. Biol. Chem. 2269-21094-21102.

    Google Scholar 

  35. Gurvits, B. Ya., Tretyakov, O. Yu., and Galoyan, A. A. 1998. Identification of macrophage migration inhibitory factor in bovine hypothalamus. International Symposium “Protein structure, stability and folding. Fundamental and medical aspects”. Moscow, Russia.

  36. Thurman, G. B., Rossio, J. L., and Goldstein, A. L. 1977. Thymosin-induced enhancement of MIF production by peripheral blood lymphocytes of thymectomized guinea pigs. In: Regulation mechanismsin lymphocyte activation, ed. By D. O. Lucas. Academic Press. N.Y.P.629-631.

    Google Scholar 

  37. Galoyan, A. A., Chailian, S. G., and Abrahamian, G. E. 1992. The role of Tβ1 in the regulation of Ca2+and calmodulin-sensitive processes (regulation of PDE activity). Neurochem. (USSR). 11:10-20.

    Google Scholar 

  38. Galoyan, A. A. and Sahakian, F. M. 1971. Isolation of cor-nary vasodilating hormones from neurosecretory granules. Docl. Acad. Nauk SSSR. 201:843-845.

    Google Scholar 

  39. Kaye, J., Porcelli, S., Tite, J., Jones, B., and Janeway, C. A. Jr. 1983. Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T-cells. J. Exp. Med. 158:836-856.

    Google Scholar 

  40. Seratte, S. A., Schulof, R. S., Leondaridis, L., Goldstein, A. L., and Sztein, M. B. 1987. Modulation of human natural killer cell cytotoxic activity, lymphokine production and interleukin-2 receptor expression by thymic hormones. J. Immunol. 139: 2338-2343.

    Google Scholar 

  41. Aarden, L. A., De Groot, E. R., Schaap, O. L., and Lansdorp, P. M. 1987. Production of hybridoma growth factor by human monocytes. Eur. J. Immunol. 10:1411-1416.

    Google Scholar 

  42. Ruff, M. R. and Gifford, G. E. 1980. Purification and physicochemical characterization of rabbit tumor necrosis factor. J. Immunol. 125:1671-1677.

    Google Scholar 

  43. Aloisi, F., Penna, G., Cerase, J., Iglesias, B. M., and Adorini, L. J. Immunol. 159: 1604-1613.

  44. Virgin, H. W., Kurt-Jones, E. A., Wittenberg, G. F., and Unanue, E. R. 1985. J. Immunol. 135:37-44.

    Google Scholar 

  45. Galoyan, A. A., Aprikian, V. S., Markossian, K. A., and Gurvits, B. Ya. 1998. Neurosecretion of cytokines by magnocellular cells of hypothalamus. Neurochem. (RAS & NAS RA). 15:361-372.

    Google Scholar 

  46. Markossian, K. A., Gurvits, B. Ya., and Galoyan, A. A. 1999. Isolation and identification of novel peptides from secretory granules of neurohypophysis. Neurochem. 16:22-25.

    Google Scholar 

  47. Gyorgy, N., Mulchahey, J. J., Smyth, D. G., and Neill, J. D. 1988. The glycopeptide moiety of vasopressin-neurophysin precursor is neurohypophyseal prolactin releasing factor. Biochem. Biophys. Res. Commun. 151:524-529.

    Google Scholar 

  48. Smyth, D. G. and Massey, D. E. 1979. A new glycopeptide in pig, ox and sheep pituitary. Biochem. Biophys. Res. Commun. 87:1006-1010.

    Google Scholar 

  49. Holwerda, D. A. 1972. A glycopeptide from the posterior lobe of pig pituitaries. 2. Primary Structure. Eur. J. Biochem. 28:340-346.

    Google Scholar 

  50. Seidah, N. G., Benjannet, S., and Chretien, M. 1981. The complete sequence of a novel human pituitary glycopeptide homologous to pig posterior pituitary glycopeptide. Biochem. Biophys. Res. Comm. 100:901-907.

    Google Scholar 

  51. Aprikyan, V. S., Galoyan, A. A. 1999. Immunocorrecting properties of a new hypothalamic polypeptide at macrophage-associated bacterial dysfunctions. Medical Science of Armenia. XXXIX. 4.

  52. Aprikian, V. S., Chailyan, S. G., and Galoyan, A. A. 2000. Hypothalamic polypeptide enhance expression of the human growth hormone in the mice fibroblastes cultures. J. Neurochem. (RAS & NAS RA). In press.

  53. Aprikyan, V. S. and Galoyan, A. A. 1999. Immunoprotective properties of a new hypothalamic polypeptide in bacterial pathologies. Med. Sci. Armen. XXXIX. 2:23-30.

    Google Scholar 

  54. Aprikyan, V. S. and Galoyan, A. A. 1999. Antibacterial activity of a new hypothalamic polypeptide. Docl. Acad. Nauk. RA. 4.

  55. Davtyan, T. K., Muradyan, E. B., Avanessian, L. A., Alexanyan, Yu. T., Petrossyan, H. H., and Galoyan, A. A. 1998. The influence of new biologically active hypothalamic polypeptides on Interleukin-2-dependent functions of human lymphocytes in culture. Neurochem. (RAS & NAS RA) 15:45-50.

    Google Scholar 

  56. Galoyan, A. A., Kipriyan, T. K., Sarkissian, J. S., Sarkissian, E. J., Grigorian Y. Kh., Andreasian, A. S., and Chavushyan E. A. 2000. The protection of snake venom (Vipera raddei Boettger 1898) neuronal injury by the new hypothalamic neurohormone. Neurochem. Res. 25:791-800.

    Google Scholar 

  57. Galoyan, A. A., Terio, N., Berg, M. J., and Marks, N. 2000. Effects of proline-rich polypeptide (PRP) derived from neurophysin-II on caspases of murine neuroblastoma: evidence for caspase-2 and-6 activation. J. Neurochem. (RAS & NAS RA). (in press).

  58. Neuman, H., Cavalie, A., Jenne, D. E., and Wekerle, H. 1995. Induction of MHC class genes in neurons. Science 269: 549-552.

    Google Scholar 

  59. Neuman, H., Boucraut, J., Hahnel, C., Misgeld, T., and Wekerle, H. 1996. Neuronal control of MHC class II inducibility in rat astrocytes and microglia. Eur. J. Neurosci. 8:2582-2590.

    Google Scholar 

  60. Neuman, H. and Wekerle, H. 1998. Neuronal control of the immune response in the central nervous system: linking brain immunity to neurodegeneration. J. Neuropathol. Exp. Neurolog. 57:1-9

    Google Scholar 

  61. Kurschner, C. and Yuzaki, M. 1999. Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein. J. Neurosci. 7770-80.

  62. Eizenberg, O., Faber-Elman, A., Lotan, M., and Schwartz, M. 1995. Interleukin-2 transcripts in human and rodent brains: possible expression by astrocytes. J. Neurochem. 64:5. 1928-1936.

    Google Scholar 

  63. Lapchak, P. A. 1992. A role of interleukin-2 in the regulation of striatal dopaminergic function. NeuroReport. 3:165-168.

    Google Scholar 

  64. Bindoni, M., Perciavalle, V., Beretta, S., Belluardo, N., and Diamanstein, T. 1988. Interleukin 2 modifies the bioelectricactivity of some neurosecretory nuclei in the rat hypothalamus. Brain Res. 462:10-14.

    Google Scholar 

  65. McCann, S. M., Karanth, S., Kamat, A., Les Dees, W., Lyson, K., Gimeno, M. and Pettori, V. 1994. Induction by cytokines of the pattern of pituitary hormone secretion in infection. Neuroimmunomodulation 1:2-13.

    Google Scholar 

  66. Whittington, R. and Faulds, D. 1993. Interleukin-2. A review of its pharmacological properties and therapeutic use in patients with cancer. Drugs 46:446-514.

    Google Scholar 

  67. Denicoff, K. D., Durkin, T. M., Lotze, M. T., Quinlan, P. E., Davis, C. L., Listwak, S. J., Rosenberg, S. A., and Rubinow, D. R. 1989. The neuroendocrine effects of interleukin-2 treatment. J. Clin. Endocrinol. Metab. 69:402-410.

    Google Scholar 

  68. Raber, J. and Bloom, F. E. 1994. IL-2 induces vasopressin release from the hypothalamus and the amygdala: role of nitric oxide-mediated signaling. J. Neurosci. 14:6187-6195.

    Google Scholar 

  69. Caraceni, A., Martini, C., Belli, F., Mascheroni, L., Rivoltini, L., Arienti, F., and Cascinelli, N. 1993. Neuropsychological and neurophysiological assesstment of the central effects of interleukin-2 administration. Eur. J. Cancer. 29A:1266-1269.

    Google Scholar 

  70. Karanth, S. and McCann, S. M. 1991. Anterior pituitary hormone control by interleukin-2. Proc. Natl. Acad. Sci. USA 88: 2961-2965.

    Google Scholar 

  71. Hanisch, U.-K. and Quirion, R. 1996. Interleukin-2 as a neuroregulatory cytokine. Brain Res. Rev. 21:246-284.

    Google Scholar 

  72. Carrieri, P. B., Maiorino, A., Provitera, V., Soscia, E., and Parrella, O. 1992. Cytokines in the pathogenesis of multiple sclerosis. Acta Neurol. Napoli. 14:333-341.

    Google Scholar 

  73. McGeer, P. L. and McGeer, E. G. 1995. The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res. Rev. 21: 195-218.

    Google Scholar 

  74. Schulte, H. M., Bamberger, C. M., Elsen, H., Herrmann, G., Bamberger, A. M., and Barth, J. 1994. System of interleukin-1αand interleukin-2 secretion in response to acute stress and to corticotropin-releasing hormones in humans. Eur. J. Clin. Invest. 24:773-777.

    Google Scholar 

  75. Alonso, R., Chaudieu, I., Diorio, J., Krishnamurthy, A., Quirion, R., and Boksa, P. 1993. Interleukin-1-modulates evoked release of [3H] dopamine in rat cultured mesencephalic cells. J. Neurochem. 61:1284-1290.

    Google Scholar 

  76. Hanisch, U.-K., Seto, D., and Quirin, R. 1993. Modulation of hippocampal acetylcholine release: a potent central action of interleukin-2. J. Neurosci. 13:3368-3374.

    Google Scholar 

  77. Zalcman, S., Green-Johnson, J. M., Murray, L., Nance, D. M., Dyck, D., Anisman, H., and Greenberg, A. H. 1994. Cytokinespecific central monoamine alterations induced by interleukin-1,-2 and-6. Brain Res. 643:40-49.

    Google Scholar 

  78. Qiu, Y., Peng, Y., and Wang, J. 1996. Immunoregulatory role of neurotransmitters. Adv. Neuroimmunol. 6:223-231.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Galoyan, A. Neurochemistry of Brain Neuroendocrine Immune System: Signal Molecules. Neurochem Res 25, 1343–1355 (2000). https://doi.org/10.1023/A:1007656431612

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007656431612

Navigation