Published on January 1, 2018 - LinkedIn

From 30 November until 2 December, the 25th Annual Meeting of the European Charcot Foundation took place in Baveno, Italy. A total of 74 posters were presented by Young Investigators and 5 Young Investigators from the ProMyelo research team were supported with a travel grant: Christin Reinbach, Julia Nedelcu, Felix Schweiger, Felix Fischbach and Nico Teske.

Delegates of 35 years or younger (born in 1982 or after) that submitted a poster automatically participated to the Young Investigator Awards. Julia Neldecu, currently making her MD-thesis in the ProMyelo research team, was selected for the Young Investigator Award in the category “Basic Studies”.

Her study was entitled “Segmental demyelination of internodes triggers mitochondrial redistribution” Oligodendrocytes, myelin sheaths and axons form a closely linked functional network, known as the axon-myelin unit. Neuronal cell bodies, which replenish the axon with mitochondria through anterograde transport, are directly implicated in the pathophysiology of progressive Multiple Sclerosis (MS). While we know that the spatial distribution of intra-axonal mitochondria is severely disturbed in MS, underlying mechanisms are poorly understood. Specifically, to what extent loss of the myelin sheath (i.e., demyelination) per se regulates mitochondrial distribution is currently unknown. In this study, Julia first examined whether oligodendrocytes die simultaneously or sequentially, and then investigated mitochondrial distribution by means of 3D-electronmicroscopy.

During initial cuprizone-induced metabolic stress (i.e. at week 1), almost all mature oligodendrocytes express the stress marker protein ATF3 (activating transcription factor 3). 3D-EM at the stage of early demyelination (i.e. at week 3) frequently showed a complete demyelination of single internodes. Such demyelinated internodes were flanked at both sites by normally myelinated axonal segments. This allowed Julia to study to what extent focal loss of the myelin sheath affects the distribution of axonal mitochondria in one and the same axon. Individual mitochondrial volumes and mitochondrial densities were significantly increased in areas of preserved internodes compared to demyelinated axonal segments.

Julia showed that metabolic stress results in an “out of phase” degeneration of oligodendrocytes, indicating a graded – and probably regulated – oligodendrocyte vulnerability. During initial demyelination, mitochondria accumulate at internodes with a preserved myelin sheath. She concluded that loss of the myelin sheath critically contributes to mitochondrial pathology in MS.

Congratulations to this nice piece of work! Please visit her poster online.