Dual role of PINK1 in EAE onset and severity (5103)

Objectives: We evaluated the impact of mitochondrial dysfunction in experimental autoimmune encephalomyelitis (EAE). Background: Reactive oxygen species and oxidative damage are observed in normal aging brain, but are exacerbated in many neurological pathologies such as Parkinson’s Disease and multiple sclerosis (MS). In MS, immune cell infiltration and glial cell activation cause persistent inflammation and intensifies the production of ROS. A particularly susceptible target of ROS are the mitochondria of both neurons and oligodendrocytes. Oxidative damage causes, among other, mitochondrial mutation, protein and lipid oxidation and metabolic hindrance, ultimately leading to cellular death. Design/Methods: Active EAE was induced in PINK1−/− and wild-type C57BL/6 mice. Clinical evaluation was used to follow the severity. Spleen, lymph nodes and central nervous system of mice were analysed by flow cytometry to assess cellular infiltration and microglial activation at onset (days 9), peak (day 15), remission (Day 28) and chronic. Immunofluorescence was used to assess demyelination and neuronal injury. Results: Our result show that total deletion of Pink1 plays a dual role in EAE, where it initially delayed the onset of neurological symptoms and can be associated with a reduced peak, but latter increased the disease severity. Differential myeloid and lymphoid cellular infiltration were observed in lymphoid organs and CNS, with infiltrating CD4 and CD8 T cells being more pro-inflammatory in both male and female PINK1−/− mice. Conclusions: Our data suggest that PINK1 plays a dual role in the development of EAE in both male and females. Further studies will show how PINK1 deficiency influence demyelination and neuronal injury. Disclosure: Mr. Balthazard has nothing to disclose. Victoria Mamane has nothing to disclose. Helene Jamann has nothing to disclose. Audrey Daigneault has nothing to disclose. Dr. Larochelle has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene, Biogen, Novartis, Sanofi-Genzyme, Alexion, EMD-Serono, Actelion. The institution of Dr. Larochelle has received research support from Merck-EMD-Serono. Diana Matheoud has nothing to disclose.