Research Projects


mechanisms of axonal pathology following oligodendrocyte apoptosis

A principal goal of our research seeks to understand the pathological consequences of oligodendrocyte apoptosis, a process thought to initiate the development of new multiple sclerosis lesions. We have demonstrated that the loss of key symbiotic interactions between the oligodendrocyte and the axons they ensheath has profound functional consequences that occur prior to the removal of the myelin membrane, that is, in the absence of demyelination. Our findings illustrate that the genesis of axonal pathology in the absence of demyelination in recent onset disease could be induced by oligodendrocyte death or dysfunction.

 

 

Following demyelination, neural progenitor cells (NPCs) produce myelin of normal thickness, whereas oligodendrocyte progenitor cells (OPCs) produce thin myelin. b) Immunogold electron microscopy reveals that progenitor identity determines the thickness of the myelin that they regenerate following demyelination (Xing et al, 2014; J Neurosci). c) Schematic of coronal section of adult mouse brain: NPC-derived oligodendrocytes remyelinate the region of the CC proximal to the SVZ, whereas OPC-derived oligodendrocytes remyelinate the medial and lateral regions of the CC. CC, corpus callosum; LV, lateral ventricle; SVZ, subventricular zone. Scalebar = 1µm.

Following demyelination, neural progenitor cells (NPCs) produce myelin of normal thickness, whereas oligodendrocyte progenitor cells (OPCs) produce thin myelin. b) Immunogold electron microscopy reveals that progenitor identity determines the thickness of the myelin that they regenerate following demyelination (Xing et al, 2014; J Neurosci). c) Schematic of coronal section of adult mouse brain: NPC-derived oligodendrocytes remyelinate the region of the CC proximal to the SVZ, whereas OPC-derived oligodendrocytes remyelinate the medial and lateral regions of the CC. CC, corpus callosum; LV, lateral ventricle; SVZ, subventricular zone. Scalebar = 1µm.

Contribution of neural stem cells to remyelination

We recently demonstrated that the quality of myelin that is regenerated in the adult brain depends on the type of progenitor cell that is recruited to produce new oligodendrocytes. Whilst both neural progenitor cells (NPCs) and oligodendrocyte progenitor cells (OPCs) can regenerate oligodendrocytes after demyelination, only oligodendrocytes that derive from NPCs can restore myelin to a control/normal level; OPC-derived oligodendrocytes only produce thin myelin after demyelination, whereas NPCs produce myelin of similar thickness to that seen in myelinated controls

 

 

Role of electrical activity in regulating myelination

In addition to...