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

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.

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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.

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Correspondence to Haider A. Khan.

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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

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Keywords

  • Experimental autoimmune encephalomyelitis
  • Hippocampus
  • Immunolocalization
  • Cognitive deficits
  • Myeloperoxidase
  • Nitric oxide