title: UCP2 up-regulation within the course of autoimmune encephalomyelitis correlates with T-lymphocyte activation.
abstract: Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder of the central nervous system (CNS) associated with severe neurological disability. Reactive oxygen species (ROS) and mitochondrial dysfunction play a pivotal role in the pathogenesis of this disease. Several members of the mitochondrial uncoupling protein subfamily (UCP2-UCP5) were suggested to regulate ROS by diminishing the mitochondrial membrane potential and constitute therefore a promising pharmacological target for MS. To evaluate the role of different uncoupling proteins in neuroinflammation, we have investigated their expression patterns in murine brain and spinal cord (SC) during different stages of experimental autoimmune encephalomyelitis (EAE), an animal model for MS. At mRNA and protein levels we found that only UCP2 is up-regulated in the SC, but not in brain. The increase in UCP2 expression was antigen-independent, reached its maximum between 14 and 21days in both OVA and MOG immunized animals and correlated with an augmented number of CD3+T-lymphocytes in SC parenchyma. The decrease in abundance of UCP4 was due to neuronal injury and was only detected in CNS of MOG-induced EAE animals. The results provide evidence that the involvement of mitochondrial UCP2 in CNS inflammation during EAE may be mainly explained by the invasion of activated T-lymphocytes. This conclusion coincides with our previous observation that UCP2 is up-regulated in activated and rapidly proliferating T-cells and participates in fast metabolic re-programming of cells during proliferation.
authors.affiliation: Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria; Institute of Vegetative Anatomy, Charité - Universitätsmedizin Berlin, Germany. Electronic address: alina.smorodchenko@charite.de.
authors.forename: Alina
authors.initials: A
authors.lastname: Smorodchenko
authors.affiliation: Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Anne
authors.initials: A
authors.lastname: Rupprecht
authors.affiliation: Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Karoline
authors.initials: K
authors.lastname: Hilse
authors.affiliation: Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Soleman
authors.initials: S
authors.lastname: Sasgary
authors.affiliation: Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Ute
authors.initials: U
authors.lastname: Zeitz
authors.affiliation: Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Reinhold G
authors.initials: RG
authors.lastname: Erben
authors.affiliation: Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria. Electronic address: elena.pohl@vetmeduni.ac.at.
authors.forename: Elena E
authors.initials: EE
authors.lastname: Pohl
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000071246:Uncoupling Protein 2 / Q000235:genetics* / Q000276:immunology; D015854:Up-Regulation
chemical_list: C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2
keywords: Cell proliferation; Central nervous system; Metabolic re-programming of cells; Mitochondrial uncoupling proteins; Neuroinflammation; UCP4