Oxidative Stress and Lymphocyte Alterations in Chronic Relapsing Experimental Allergic Encephalomyelitis in the Rat Hippocampus and Protective Effects of an Ethanolamine Phosphate Salt
- 37 Downloads
Chronic relapsing experimental allergic encephalomyelitis (CR-EAE) exhibits neuropathological and immunological dysfunctions similar to those found in multiple sclerosis (MS) and has been used as an animal model of MS. Inflammatory infiltrates and oxidative stress have been linked to the development of both diseases. Ethanolamine plasmalogen derivates have been shown to be powerful antioxidants and immunomodulators. Therefore, the objective of this study was to analyse inflammatory infiltrates, the state of the oxidative defences and the possible protective effects of calcium, magnesium and phosphate ethanolamine (EAP) in the CR-EAE rat hippocampus. To this aim, we evaluated, by immunohistochemistry, T cell infiltrates, Iba-1+ (a marker of activated microglia) immunoreactivity and TUNEL (+) cells. We also measured the protein levels and activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GP) and glutathione reductase (GR). In addition, reduced (GSH) and oxidized (GSSG) glutathione levels, lipid peroxidation and cholesterol as well as desmosterol content were determined. We found an increase in T cell infiltrates and Iba1+ immunoreactivity, lipid peroxidation, SOD, GP and GR activities as well as enhanced cholesterol levels and a decrease in CAT activity, GSH and desmosterol levels in the first and second attack in the CR-EAE rat hippocampus. Pretreatment of CR-EAE rats with EAP led to a delay in the onset of the clinical signs of the disease as well as a decrease in inflammatory infiltrates and alterations of the antioxidant defences in the hippocampus. Altogether, the present results suggest a protective role of EAP in the CR-EAE rat hippocampus.
KeywordsCR-EAE Hippocampus Multiple sclerosis Oxidative stress Antioxidant defences Ethanolamine phosphate
We wish to thank the staff of the Animal Center of the Universidad de Alcalá for their support with the animal care and handling. CIBEROBN is an initiative of the Instituto de Salud Carlos III (ISCIII), Spain. MOIR Mechanisms of Insulin Resistance.
This work was supported by the Ministerio de Ciencia e Innovación (SAF2010-22277), (SAF2011-29951) and (S2010/BMD-2423).
Compliance with ethical standards
The animal experiments performed in the present study conform to the guidelines set by the Animal Care Committee of Alcalá University as well as to the International guidelines on the ethical use of animals set by the Council of Europe (Protection of Animals Used for Experimentation, 1986 ETS No. 123), and all experimental protocols were previously approved.
- 36.Marshall DL, De Micheli E, Bogdanov MB, Wurtman RJ (1996) Effects of ethanolamine (Etn) administration on Etn and choline (Ch) levels in plasma, brain extracellular fluid (ECF) and brain tissue, and on brain phospholipid levels in rats: an in vivo study. Neurosci Res Commun 18:87–96CrossRefPubMedGoogle Scholar
- 57.Abourbeh G, Thézé B, Maroy R, Dubois A, Brulon V, Fontyn Y, Dollé F, Tavitian B et al (2012) Imaging microglial/macrophage activation in spinal cords of experimental autoimmune encephalomyelitis rats by positron emission tomography using the mitochondrial 18 kDa translocator protein radioligand [18F]DPA-714. J Neurosci 32:5728–5736CrossRefPubMedPubMedCentralGoogle Scholar
- 60.Hampton DW, Anderson J, Pryce G, Irvine KA, Giovannoni G, Fawcett JW, Compston A, Franklin RJ et al (2008) An experimental model of secondary progressive multiple sclerosis that shows regional variation in gliosis, remyelination, axonal and neuronal loss. J Neuroimmunol 201-202:200–211CrossRefPubMedGoogle Scholar
- 65.MacMicking JD, Willenborg DO, Weidemann MJ, Rockett KA, Cowden WB (1992) Elevated secretion of reactive nitrogen and oxygen intermediates by inflammatory leukocytes in hyperacute experimental autoimmune encephalomyelitis: enhancement by the soluble products of encephalitogenic T cells. J Exp Med 176:303–307CrossRefPubMedGoogle Scholar
- 74.Singh I, Paintlia AS, Khan M, Stanislaus R, Paintlia MK, Haq E, Singh AK, Contreras MA (2004) Impaired peroxisomal function in the central nervous system with inflammatory disease of experimental autoimmune encephalomyelitis animals and protection by lovastatin treatment. Brain Res 1022:1–11CrossRefPubMedGoogle Scholar
- 78.Zargari M, Allameh A, Sanati MH, Tiraihi T, Lavasani S, Emadyan O (2007) Relationship between the clinical scoring and demyelination in central nervous system with total antioxidant capacity of plasma during experimental autoimmune encephalomyelitis development in mice. Neurosci Lett 412:24–28CrossRefPubMedGoogle Scholar
- 79.Calabrese V, Scapagnini G, Ravagna A, Bella R, Butterfield DA, Calvani M, Pennisi G, Giuffrida Stella AM (2003) Disruption of thiol homeostasis and nitrosative stress in the cerebrospinal fluid of patients with active multiple sclerosis: evidence for a protective role of acetylcarnitine. Neurochem Res 28:1321–1328CrossRefPubMedGoogle Scholar
- 82.Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC, Mattson MP (2004) Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer’s disease. Proc Natl Acad Sci U S A 101:2070–2075CrossRefPubMedPubMedCentralGoogle Scholar
- 90.Waterham HR, Koster J, Romeijn GJ, Hennekam RC, Vreken P, Andersson HC, FitzPatrick DR, Kelley RI et al (2001) Mutations in the 3beta-hydroxysterol Delta24-reductase gene cause desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis. Am J Hum Genet 69:685–694CrossRefPubMedPubMedCentralGoogle Scholar