Mitochondrial Dysfunction in EAE Mice Brains and Impact of HIF1-α Induction to Compensate Energy Loss

 Mitochondrial dysfunction may be involved in the process of degradation and death of gray matter cells of the central nervous system (CNS) in patients with multiple sclerosis (MS). MS is known as a chronic, progressive demyelinating disease of the CNS.

 Experimental autoimmune encephalomyelitis (EAE) mouse model of MS is the best method for extracting data trend for diagnosing this disorder. The aim of this study was to evaluate the specific activity of the Cytochrome oxidase (COX), ATP, and hypoxia-inducible factor 1 alpha (HIF-1α) in brain tissues of the EAE mice model.

 Twenty-one female mice (C57BL/6) were used, 9 for inducing the EAE model and 6 for each of both negative and sham control groups. The specific activity of the COX, ATP, and HIF-1α levels were evaluated in the whole brain of all 3 mice groups.

 According to the findings, specific COX activity and ATP levels were decreased significantly, which could be due to the mitochondrial dysfunction and neuronal loss in MS lesions, whereas HIF-1α levels increased significantly in the EAE mice group, compared to the sham and negative control groups. The significant increase of HIF-1α levels reinforces 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.

 The results of this study suggest that HIF-1α induction may also be a potential target for controlling the progression of MS, or the development of HIF-1α inducing compounds could be a potential candidate for the management of this disease and provide a rationale to conduct further research in this area.