title: Accumulation of reactivity to MBP sensitizes TRAIL mediated oligodendrocyte apoptosis in adult sub cortical white matter in a model for human multiple sclerosis.
abstract: Reactivity to myelin associated proteins is the hallmark of human multiple sclerosis (M.S) and its experimental counterparts. However, the nature of such reactivity has not been described fully. Herein, we report that myelin basic protein (MBP) reactivity accumulates in a rat model for M.S. over a period of time and sensitizes TRAIL mediated progressive oligodendrocyte apoptosis. We used active immunization by Myelin Oligodendrocyte Glycoprotein (MOG, 50 μg) to study chronic remitting relapsing encephalomyelitis in rats. A time point analysis of the progressive disease revealed cumulative accumulation of anti myelin basic protein antibodies during the disease progression with minimal change in the anti-MOG antibodies. Increased reactivity to MBP was studied to sensitize TNF related apoptosis-inducing ligand (TRAIL) and other proinflammatory cytokines in a cumulative fashion leading to the Caspase dependent apoptosis of oligodendrocytes and myelin loss. In a rescue experiment, we could limit the demyelination and prevent disease progression by neutralizing the effector, TRAIL in an early stage of the disease. This is the first study to identify the accumulation of MBP antibodies in MOG induced EAE which possibly leads to TRAIL sensitized oligodendrocyte apoptosis in the white mater of EAE rats. This finding stresses on the need to study MBP antibody titers in M.S. patients and therefore might serve as an alternate marker for progressive demyelination.
authors.affiliation: Clinical Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062, India. elham_82@rediffmail.com.|School of Medicine, University of Kentucky, 741 S Limestone St., Lexington, KY, 40536, USA. elham_82@rediffmail.com.
authors.forename: Sajad
authors.initials: S
authors.lastname: Mir
authors.affiliation: Department of Medical Elementology and Toxicology, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062, India.
authors.forename: Farrah
authors.initials: F
authors.lastname: Ali
authors.affiliation: Department of Medical Elementology and Toxicology, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062, India.
authors.forename: Deepika
authors.initials: D
authors.lastname: Chauhan
authors.affiliation: Radiation Biology Division, Institute of Nuclear Medicine and Allied Sciences (INMAS), New Delhi, 110054, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Arora
authors.affiliation: Clinical Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062, India.
authors.forename: Haider A
authors.initials: HA
authors.lastname: Khan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000378:metabolism*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology*; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism; D066127:White Matter / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein
keywords: Demyelination; EAE; MBP; Multiple sclerosis, autoimmunity, neuroinflammation; Trail