Skip to main content

Advertisement

SpringerLink
Log in

Hippocampal neurodegeneration in experimental autoimmune encephalomyelitis (EAE): potential role of inflammation activated myeloperoxidase

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Experimental Autoimmune Encephalomyelitis (EAE) is a well-established animal model of human multiple sclerosis (MS). The effect of this inflammatory disease on hippocampus has not been addressed. Keeping in view the above consideration an attempt was made to delineate the effect of EAE on the hippocampus of Wistar rats. The assessment of the damage to the hippocampus was done 16 days post induction by the immunolocalization of ChAT (choline acetyl transferase). ChAT decreased remarkably after induction that revealed cholinergic neuronal degeneration in the hippocampus. Subsequently, many biochemical parameters were assessed to ascertain inflammatory activation of nitric oxide and associated oxidative damage as a putative mechanism of the cholinergic degeneration. Nitric oxide metabolites increased significantly (P < 0.05) with enhancement of MPO (Myeloperoxidase activity) (P < 0.001) in the MOG (myelin oligodendrocyte protein) group as compared to the controls. Peroxidation of biomembranes increased (P < 0.001), while reduced glutathione depleted (P < 0.001) with parallel decrease in catalase (P < 0.01) and superoxide dismutase enzyme activity (P < 0.001) in the MOG group. Our results show a strong role of peroxidase dependent oxidation of nitrite and oxidative stress in cholinergic degeneration in EAE.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Gay D, Esiri M (1991) Blood-brain barrier damage in acute multiple sclerosis. Brain 114:557–572. doi:10.1093/brain/114.1.557

    Article  PubMed  Google Scholar 

  2. AlOmaishi J, Bashir R, Gendelman HE (1999) The cellular immunology of multiple sclerosis. J Leukoc Biol 65:444–452

    CAS  Google Scholar 

  3. Benveniste EN (1997) Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J Mol Med 75:165–173. doi:10.1007/s001090050101

    Article  PubMed  CAS  Google Scholar 

  4. Martiney JA, Cuff C, Litwak M, Berman J, Brosnan CF (1998) Cytokine induced inflammation in the central nervous system revisited. Neurochem Res 23:349–359. doi:10.1023/A:1022457500700

    Article  PubMed  CAS  Google Scholar 

  5. Hendriks JJA, Teunissen CE, de Vries HE, Dijkstra CD (2005) Macrophages and neurodegeneration. Brain Res Brain Res Rev 48:185–195. doi:10.1016/j.brainresrev.2004.12.008

    Article  PubMed  CAS  Google Scholar 

  6. Castano A, Herrera AJ, Cano J, Machado (1998) A lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal dopaminergic system. J Neurochem 70:1584–1592

    Article  PubMed  CAS  Google Scholar 

  7. Peyser JM, Edwards KR, Poser CM, Filskov SB (1980) Cognitive function in patients with multiple sclerosis. Arch Neurol 37:577–579

    PubMed  CAS  Google Scholar 

  8. Rao SM, Leo GL, Bernardin L et al (1991) Cognitive dysfunction in MS. Frequency, patterns and prediction. Neurology 41:685–691

    PubMed  CAS  Google Scholar 

  9. Bobholz JA, Rao SM (2003) Cognitive dysfunction in multiple sclerosis: a review of recent developments. Curr Opin Neurol 16:283–288. doi:10.1097/00019052-200306000-00006

    Article  PubMed  Google Scholar 

  10. Gaudino EA, Chiaravalloti ND, De Luca J, Diamond BJ (2001) A comparison of memory performance in relapsing-remitting, primary progressive and secondary progressive, multiple sclerosis. Neuropsychiatry Neuropsychol Behav Neurol 14:32–44

    PubMed  CAS  Google Scholar 

  11. Manns JR, Hopkins RO, Reed JM, Kitchener EG, Squire LR (2003) Recognition memory and the human hippocampus. Neuron 37:171–180. doi:10.1016/S0896-6273(02)01147-9

    Article  PubMed  CAS  Google Scholar 

  12. Poluektova L, Meyer V, Walters L, Paez X, Gendelman HE (2005) Macrophage-induced inflammation affects hippocampal plasticity and neuronal development in a murine model of HIV-1 encephalitis. Glia 52:344–355. doi:10.1002/glia.20253

    Article  PubMed  Google Scholar 

  13. D’Intino G, Paradisi M, Fernandez M, Giuliani A, Aloe L, Giardino L, Calza L (2005) Cognitive deficit associated with cholinergic and nerve growth factor down-regulation in experimental allergic encephalomyelitis in rats. Proc Natl Acad Sci USA 102:3070–3075. doi:10.1073/pnas.0500073102

    Article  PubMed  CAS  Google Scholar 

  14. Sicotte NL, Kern KC, Giesser BS, Arshanapalli A, Schultz A, Montag M, Wang H, Bookheimer SY (2008) Regional hippocampal atrophy in multiple sclerosis. Brain 131:1134–1141. doi:10.1093/brain/awn030

    Article  PubMed  CAS  Google Scholar 

  15. Gray E, Taya TL, Betmouni S, Scolding N, Love S (2007) Elevated activity and microglial expression of myeloperoxidase in demyelinated cerebral cortex in multiple sclerosis. Brain Pathol 18:86–95. doi:10.1111/j.1750-3639.2007.00110.x

    Article  PubMed  Google Scholar 

  16. Agrawal AK, Shukla S, Chaturvedi RK, Seth K, Srivastava N, Ahmad A, Seth PK (2004) Olfactory ensheathing cell transplantation restores functional deficits in rat model of Parkinson’s disease: a cotransplantation approach with fetal ventral mesencephalic cells. Neurobiol Dis 16:516–526. doi:10.1016/j.nbd.2004.04.014

    Article  PubMed  CAS  Google Scholar 

  17. Bradley PP, Priebat DA, Christensen RD, Rothstein G (1982) Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78:206–209. doi:10.1111/1523-1747.ep12506462

    Article  PubMed  CAS  Google Scholar 

  18. Bohme DH, Kosechi R, Carsen S, Stern F, Marks N (1977) Lipoperoxidation in human and rat brain tissue: developmental and regional studies. Brain Res 136:11–21. doi:10.1016/0006-8993(77)90127-5

    Article  Google Scholar 

  19. Sedlak J, Linsay RH (1968) Estimation of total protein bound and nonprotein bound sulphydryl group in tissue with Ellman’s reagents. Anal Biochem 25:192–205. doi:10.1016/0003-2697(68)90092-4

    Article  PubMed  CAS  Google Scholar 

  20. Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 21:130–132

    PubMed  CAS  Google Scholar 

  21. Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394. doi:10.1016/0003-2697(72)90132-7

    Article  PubMed  CAS  Google Scholar 

  22. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. doi:10.1016/0003-2697(76)90527-3

    Article  PubMed  CAS  Google Scholar 

  23. Jarrard LE, Meldrum BS (2008) Selective excitotoxic pathology in rat hippocampus. Neuropathol Appl Neurobiol 19:381–389. doi:10.1111/j.1365-2990.1993.tb00458.x

    Article  Google Scholar 

  24. Moromoto K, Murasugi T, Oda T (2002) Acute neuroinflammation exacerbates excitotoxicity in rat hippocampus in vivo. Exp Neurol 177:95–104. doi:10.1006/exnr.2002.7991

    Article  CAS  Google Scholar 

  25. Pitt D, Werner P, Raine CS (2000) Glutamate excitotoxicity in a model of multiple sclerosis. Nat Med 6:67–70. doi:10.1038/71555

    Article  PubMed  CAS  Google Scholar 

  26. Stone LA, Smith ME, Albert PS, Bash CN, Maloni H, Frank JA, McFarland HF (1995) Blood-brain barrier disruption on contrast-enhanced MRI in patients with mild relapsing-remitting multiple sclerosis: relationship to course, gender, and age. Neurology 45:1122–1126

    PubMed  CAS  Google Scholar 

  27. Bredt DS, Hawing PH, Snyder SH (1990) Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 347:768–770. doi:10.1038/347768a0

    Article  PubMed  CAS  Google Scholar 

  28. Zaffaroni M (2003) Biological indicators of the neurodegenerative phase of multiple sclerosis. Neurol Sci 24:279–282. doi:10.1007/s10072-003-0174-3

    Article  Google Scholar 

  29. Beckman JS (1996) Oxidative damage and tyrosine nitration from peroxynitrite. Chem Res Toxicol 9:836–844. doi:10.1021/tx9501445

    Article  PubMed  CAS  Google Scholar 

  30. Liu JS, Zhao ML, Brosnan CF, Lee SC (2001) Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions. Am J Pathol 158:2057–2066

    PubMed  CAS  Google Scholar 

  31. Van der Vliet A, Eiserich JP, Halliwell B, Cross CE (1997) Formation of reactive nitrogen species during peroxidase-catalyzed oxidation of nitrite. A potential additional mechanism of nitric oxide dependent toxicity. J Biol Chem 272:7617–7625. doi:10.1074/jbc.272.12.7617

    Google Scholar 

Download references

Acknowledgments

Authors are thankful to Dr. G. N. Qazi (Vice Chancellor, Jamia Hamdard) for continuous support during this study. Mir Sajad is recipient of Senior Research Fellowship (SRF) from Ministry of Health and Family Welfare, Government of India, New Delhi.

Author information

Authors and Affiliations

  1. Developmental Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, 110062, India

    Mir Sajad, Jamil Zargan, Sadiq Umar & Haider A. Khan

  2. Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences (INMAS), New Delhi, 110054, India

    Raman Chawla

  3. Department of Internal Medicine, SKIMS Medical College Hospital, Bemina, Srinagar, 190018, India

    Mir Sadaqat

Authors
  1. Mir Sajad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jamil Zargan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raman Chawla
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sadiq Umar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mir Sadaqat
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Haider A. Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Haider A. Khan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sajad, M., Zargan, J., Chawla, R. et al. Hippocampal neurodegeneration in experimental autoimmune encephalomyelitis (EAE): potential role of inflammation activated myeloperoxidase. Mol Cell Biochem 328, 183–188 (2009). https://doi.org/10.1007/s11010-009-0088-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-009-0088-3

Keywords

Search

Navigation