Elevation of HIF-1α in whole brain of the animal model of Multiple Sclerosis may be a potential target for controlling of this disease

Background and Aim : Experimental autoimmune encephalomyelitis (EAE) is the best known and available animal model of multiple sclerosis (MS) and useful model for studying the mechanisms of this disease and other autoimmune disorders. A plenty of evidence indicated that mitochondrial dysfunction may be involved in cell death of white and gray matters of CNS in the patients with MS. The aim of this study was to evaluate specific activity of the cytochrome oxidase (COX), ATP, and hypoxia-inducible factor 1 alpha (HIF-1α) in whole brain tissues of the EAE mouse model of MS disease.Methods : Nine mice for inducing EAE model using Hooke kit, EK-2110, MOG 35-55/CFA emulsion, Pertossis toxin (PTX), 6 mice as the control group (with CFA and PTX injections) and 6 mice as the sham group (with injection with PBS). Measurement of specific COX activity, ATP and HIF-1α levels were performed in all of the mice’s brain tissues.Results : The data indicated that specific COX activity and ATP levels were decreased significantly in EAE mice, whereas HIF-1α levels increased significantly in EAE compared to the sham and negative control mice. Decreasing COX activity and ATP levels could be due to the mitochondrial dysfunction in whole brains of the EAE mice and an imbalance between energy demands might be additional reason for neuronal loss in MS lesions. Meanwhile, significant elevation levels of HIF-1α in the hypoxia-like injuries of EAE mice brains reinforce the hypothesis that the HIF-1α induction may provide prevention of neuronal death by compensating energy loss under hypoxia-like conditions in EAE mice brains.Conclusion : This preliminary study concluded that the HIF-1α induction in whole brains of EAE mice model of MS may be a potential target for controlling of progression of the MS disease.

کلیدواژه ها:

Multiple Sclerosis ، EAE ، Cytochrome oxidase ، ATP ، HIF-1α