Skip to main content
SpringerLink
Log in

Neuroimmunological correlates of cognitive impairment

  • Cognitive Dysfunction in MS
  • Published:
The Italian Journal of Neurological Sciences Aims and scope Submit manuscript

Abstract

The few available data on the immunological correlates of cognitive impairment occurring in neurological diseases are reviewed in order to provide a rationale for preliminary investigations in multiple sclerosis. Since HIV-correlated dementia constitutes a paradigmatic example of immune-mediated cognitive impairment, the neurodegenerative mechanisms occurring in such disease as well as in Alzheimer's disease are illustrated. The role of antibody-mediated immune responses, of microglial cells and of certain cytokines, particularly interleukin-1, in excitotoxic neural degeneration are put in evidence.

Sommario

I pochi dati disponibili circa i correaaai immunologici dei disturbi cognitivi in corso di malattie neurologiche vengono presi in rassegna al fine di delineare un razionale per eventuali indagini preliminari anche nell'ambito della sclerosi multipla. Poiché la demenza correlata all'infezione da HIV costituisce un esempio paradigmatico di deficit cognitivo immuno-mediato, vengono illustrati i mechanismi di neurodegenerazione the intervengono in tale condizione cosi come nella malattia di Alzheimer. Vengono evidenziati i ruoli della risposta immunitaria anticorpo-mediata, della microglia e di talune citochine, in particolare interleuchina-1, nel processo di neurodegenerazione da eccitotossicitd.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mehler MF, Goldstein H, Kessler JA (1996) Effect of cytokines on CNS cells: Neurons. In: Ransohoff RM, Benveniste EN (eds) Cytokines and the CNS. CRC, Boca Raton, pp 115–150

    Google Scholar 

  2. Hopkins SJ, Rothwell NJ (1995) Cytokines and the nervous system 1: Expression and recognition. Trends Neurol Sci 18:83–88

    Google Scholar 

  3. Hopkins SJ, Rothwell NJ (1995) Cytokines and the nervous system II: Actions and mechanisms of action. Trends Neurol Sci 18:138–136

    Google Scholar 

  4. Lees GJ (1993) Contributory mechanisms in the causation of neurodegenerative disorders. Neuroscience 54:287–322

    Google Scholar 

  5. Beal MF (1994) Molecular mechanisms of excitotoxicity. In: Racagni G, Brunello N, Langer SZ (eds) Recent advances in the treatment of neurodegenerative disorders and cognitive dysfunction. Karger, Basel, pp 102–111

    Google Scholar 

  6. Rothwell NJ, Loddick S, Lawrence C (1995) Cytokines and neurodegeneration. In: Rothwell NJ (ed) Immune responses in the nervous system. BIOS, Oxford, pp 77–99

    Google Scholar 

  7. Rothwell NJ, Strijbos PJ (1995) Cytokines in neurodegeneration and repair. Int J Dev Neurosci 13:179–185

    Google Scholar 

  8. Loddick SA, Wong ML, Bongiorno PB, Gold PW Licinio J, Rothwell NJ (1997) Endogenous interleukin-1 receptor antagonist is neuroprotective. Biochem Biophys Res Commun 234:211–225

    Google Scholar 

  9. Loddick SA, McKenzie A, Rothwell NJ (1996) An ICE inhibitor, z-VAD-DCB attenuates ischaemic brain damage in the rat. Neuroreport 7:1465–1468

    Google Scholar 

  10. Strijbos PJ, Rothwell NJ (1995) Interleukin-1 attenuates excitatory amino acid induced neurodegeneration in vitro: Involvement of nerve growth factor. J Neurosci 15:3468–3474

    Google Scholar 

  11. Lechan RM, Toni R, Clark BD, Cannon JC, Shaw AR, Dinarello CA, Reichlin S (1990) Immunoreactive interleukinlb localization in the rat forebrain. Brain Res 514:135–140

    Google Scholar 

  12. Giulian D (1993) Reactive glia as rivals in regulating neuronal survival. Glia 7:102–110

    Google Scholar 

  13. Piani D, Frei K, Schaffner A, Fontana A (1992) Macrophageinduced cytotoxicity of NMDA receptor positive neurons involves excitatory amino acids rather than reactive oxygen intermediates or cytokines. Eur Immunol 22:2429–2436

    Google Scholar 

  14. Banati RB, Gehrmann J, Schubert P, Kreutzberg GW (1993) Cytotoxicity of microglia. Glia 7:111–118

    Google Scholar 

  15. Dickson DW, Lee SC, Brosnan CF, Sinicropi S, Vlassara H, Yen SC (1996) Neuroimmunology of aging and Alzheimer's disease with emphasis on cytokines. In: Ransohoff RM, Benveniste EN (eds) Cytokines and the CNS. CRC, Boca Raton, pp 257–267

    Google Scholar 

  16. McGeer PL, Akiyama H, Itagaki S, McGeer EG (1989) Immune system response in Alzheimer's disease. Can J Neurol Sci 16:516–527

    Google Scholar 

  17. Rogers J, Kirby LC, Hempleman SR, Berry DL, McGeer PL, Kaszniak AW, Zalinski J, Cofield M, Mansukhani L, Willson P, Kogan F (1993) Clinical trial of indomethacin in Alzheimer's disease. Neurology 43:1609–1616

    Google Scholar 

  18. McGeer PL, Itagaki S, Tago H (1987) Reactive microglia in patients with senile dementia of the Alzheimer's type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett 79:195–200

    Google Scholar 

  19. Boje K, Arora PK (1992) Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death. Brain Res 587:250–256

    Google Scholar 

  20. Styren SD, Civin WH, Rogers J (1990) Molecular, cellular, and pathologic characterization of HLA-DR immunoreactivity in normal elderly and Alzheimer's disease brain. Exp Neurol 110:93–100

    Google Scholar 

  21. Dickson DW, Lee SC, Mattiace LA, Yen SH, Brosnan CF (1993) Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. Glia 7:75–82

    Google Scholar 

  22. Rothwell NJ, Relton JK (1993) Involvement of cytokines in acute neurodegeneration in the CNS. Neurosci Biobehav Rev 17:217–227

    Google Scholar 

  23. Soininen H, Heinonen O, Hallikainen M, Hanninen T, Koivisto K, Syrjanen S, Talasniemi S, Riekkinen PJ (1993) Circulating immune complexes in sera from patients with Alzheimer's disease and subjects with age-associated memory impairment. J Neural Transmission 6:179–188

    Google Scholar 

  24. Kell SH, Allman RM, Harrel LE, Liu T, Solvason N (1996) Association between Alzheimer's disease and bound autochthonous IgM on T cells. J Am Ger Soc 44:1362–1365

    Google Scholar 

  25. McRae A (1996) Microglial cerebrospinal fluid antibodies. Significance for Alzheimer disease. Mol Chem Neuropathol 28:89–95

    Google Scholar 

  26. Oron L, Dubovik V, Novitsky L, Eilam D, Michaelson DM (1997) Animal model and in vitro studies of anti-neurofilament antibodies mediated neurodegeneration in Alzheimer's disease. J Neural Transm Suppl 49:77–84

    Google Scholar 

  27. Pasinetti GM (1996) Inflammatory mechanisms in neurodegeneration and Alzheimer's disease: the role of the complement system. Neurobiol Aging 17:707–716

    Google Scholar 

  28. Nottet HS, Flanagan EM, Flanagan CR, Gelbard HA, Gendelman HE, Reinhard JF Jr (1996) The regulation of quinolinic acid in human immunodeficiency virus/infected monocytes. J Neurovirol 2:111–117

    Google Scholar 

  29. Meillet D, Belec L, Celton N, Gervais A, Reboul J, Gentilini M, Delattre J, Schuller E (1993) Intrathecal synthesis of beta 2-microglobulin and lysozyme: Differential markers of nervous sys tem involvement in patients infected with human immunodeficiency virus type 1. Eur J Clin Chem Biochem 31:609–615

    Google Scholar 

  30. Perrella O, Finelli L, Munno I, Perrella A, Soscia E, Carrieri PB (1993) Cerebrospinal fluid ferritin in human immunodeficiency virus infection: A marker of neurologic involvement? J Infect Dis 168:1079–1082

    Google Scholar 

  31. Griffin DE, Wesselingh S, McArthur JC (1994) Elevated central nervous system prostaglandins in HIV-associated dementia. Ann Neurol 35:592–597

    Google Scholar 

  32. Fuchs D, Chiodi F, Albert J, Asjo B, Hagberg L, Hausen A, Norkrans G, Reinbnegger G, Werner E, Wachter H (1989) Neopterin concentrations in cerebrospinal fluid and serum of individuals infected with HIV-1. AIDS 3:285–289

    Google Scholar 

  33. Wesselingh SL, Tyor WR, Griffin DE (1996) Cytokines and HIV associated dementia. In: Ransohoff RM, Benveniste EN (eds) Cytokines and the CNS. CRC, Boca Raton, pp 286–307

    Google Scholar 

  34. Genis P, Jett M, Bernton EW, Boyle T, Gelbard H, Dzenko K, Keane RW, Resnick L, Mizrachi Y, Volsky DJ, Epstein LG, Gendelman HE (1992) Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophages-astroglia interactions: Implications for the neuropathogenesis of HIV disease. J Exp Med 176:1703–1710

    Google Scholar 

  35. Malessa R, Heimbach M, Brockmeyer NH, Hengge U, Rascher W, Michel MC (1996) Increased neuropeptide Ylike immunoreactivity in cerebrospinal fluid and plasma of human immunodeficiency virus/infected patients: Relationships to HIV encephalopathy. J Neurol Sci 136:154–158

    Google Scholar 

  36. Sonti G, Ilyn SE, Plata-Salaman CR (1996) Neuropeptide Y blocks and reverses IL-lb-induced anorexia in rats. Peptides 17:517–520

    Google Scholar 

  37. Cantell K, Pullkien E, Eluoso R, Suominen J (1980) Effects of interferon on severe psychiatric diseases. Ann Clin Res 12:131–132

    Google Scholar 

  38. Pliskin NH, Hamer DP, Goldstein DS, Towle VL, Reder AT, Noronha A, Arnason BG (1996) Improved delayed visual reproduction test performance in multiple sclerosis patients receiving interferon beta-lb. Neurology 6:1463–1468

    Google Scholar 

  39. Fischer JS, Priore R, Jacobs D, et al. and the MSCRG (1998) Neuropsychological effects of Avonex (Interferon-β-1 a) in relapsing multiple sclerosis. Neurology 50[Suppl 4]:32–33 (abstract)

    Google Scholar 

  40. Pliskin NH, Reder AT, Goldstein DS (1997) Neuropsychological effects of interferon therapy. In: Reder AT (ed) Interferon therapy of multiple sclerosis. Marcel Dekker, New York, pp 139–160

    Google Scholar 

  41. Traugott U (1998) Detailed analysis of immunomodulatory properties of Fluoxetine (PROZAC) in chronic experimental allergic encephalomyelitis in SJL/J mice. Neurology 50 [Suppl 4]: 105–106 (abstract)

    Google Scholar 

  42. Bianchi M, Rossoni, Sacerdote P, Panerai AE, Berti F (1995) Carbamazepine exerts anti-inflammatory effects in the rat. Eur J Pharmacol 294:71–74

    Google Scholar 

  43. Klein TW, Newton C, Friedman H (1998) Cannabinoid receptors and immunity. Immunol Today 8:373–381

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Multiple Sclerosis Research Center Gallarate Hospital, University of Milano, Via Pastori 4, I-21013, Gallarate, (VA), Italy

    M. Zaffaroni

Authors
  1. M. Zaffaroni
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zaffaroni, M. Neuroimmunological correlates of cognitive impairment. Ital J Neuro Sci 19 (Suppl 6), S418–S423 (1998). https://doi.org/10.1007/BF00539599

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00539599

Key words

Search

Navigation