Key words: Spinal Cord, MRI, Amyotrophic Lateral Sclerosis, (Ultra) High Field, Longitudinal
Follow-up

This project focuses on the evaluation of early tissue impairment encountered in the context of Amyotrophic Lateral Sclerosis by taking advantages of potentialities offered by both ultra-high field Magnetic Resonance Imaging (7T) and electrophysiological measurements. The project is based on the already existing close collaboration between CRMN-SLA (Pr. S. Attarian and Dr. A. Verschueren) and CRMBM-CEMEREM (V. Callot’s team).

This research aimed to better understand the link between inflammation and mitochondrial dysfunction in Chagas disease cardiomyopathy (CCC). This neglected disease is caused by the parasite Trypanosoma cruzi and it affects people from Europe, North and South America (where it is endemic). The heart of CCC patients is an inflammatory milieu, rich of interferon-gamma (IFN-γ) and tnf-alpha (TNF-α), which cause damage to the heart, impairing blood pump. Indeed, CCC patients have lower survival rate compared to patients with other cardiomyopathies. Previous data of our group revealed an accumulation of polymorphisms in mitochondrial genes in CCC patients and we raised the hypothesis that mitochondrial dysfunction and excessive inflammation play together to damage the cardiac cells (cardiomyocytes) and thus worsening the disease. In this work, we found that the hearts of CCC patients have decreased number of mitochondrial DNA and higher quantity of nitrite and nitrotyrosine, markers of nitro-oxidative stress. In a similar manner, cardiac cells exposed to IFN-γ and TNF-α have also increased nitro-oxidative stress and decreased number of mitochondrial DNA. Additionally, the cytokines also impaired mitochondrial function of cardiac cells, as observed in changes of oxygen consumption and depleted ATP production. This work provides relevant data to support association between mitochondria dysfunction and CCC, reinforcing new studies targeting mitochondria as a novel strategy for CCC therapy.