Abstract Details

Title Dual role of PINK1 in EAE onset and severity

Topic Multiple Sclerosis

Presentation(s) MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 129

Objective

Objectives: We evaluated the impact of mitochondrial dysfunction in experimental autoimmune encephalomyelitis (EAE).

Background 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

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

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

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.

Authors/Disclosures
Renaud Balthazard (CRCHUM) PRESENTER	Mr. Balthazard has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Catherine Larochelle, MD (CRCHUM)	Dr. Larochelle has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Novartis, Sanofi-Genzyme, Alexion, EMD-Serono, FIND therapeutics, Actelion. The institution of Dr. Larochelle has received research support from Université de Montréal-CHUM.
	No disclosure on file

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