UCP2 up-regulation within the course of autoimmune encephalomyelitis correlates with T-lymphocyte activation

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2017-04, Vol.1863 (4), p.1002-1012
• Main Authors: Smorodchenko, Alina, Schneider, Stephanie, Rupprecht, Anne, Hilse, Karoline, Sasgary, Soleman, Zeitz, Ute, Erben, Reinhold G., Pohl, Elena E.
• Format: Article
• Language: English
• Subjects: Cell proliferation; Central nervous system; Metabolic re-programming of cells; Mitochondrial uncoupling proteins; Neuroinflammation; UCP4
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2017.01.019

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. •UCP2 expression correlates with the extent of lymphocytes invasion in spinal cord and is antigen-independent.•The maximum of UCP2 expression coincides with the peak of the active EAE.•The expression of UCP4 in neurons is not affected within the course time of disease.