The role of SVZ-derived neural precursors in demyelinating diseases: from animal models to multiple sclerosis.
We will review the role of endogenous neural stem cells in myelin repair both in animal models of demyelination and multiple sclerosis. The mammalian sub-ventricular zone (SVZ) is the largest germinative zone of the adult brain, which contains a well characterized stem cell niche. While most studies highlight the neurogenic potential of SVZ progenitors, recent data indicate that SVZ cells become reactived in response to different pathological cues, like trauma, ischemia, neurodegeneration, inflammation and demyelination. Experimental models of demyelination in rodent demonstrate enhanced proliferation and recruitment of SVZ progenitors into myelin lesions, in response to demyelination. Moreover, cell lineage tracing experiments showed that SVZ progenitor cells can give rise to oligodendrocytes in demyelinated lesions, that could potentially contribute to remyelination. To examine the relevance of these studies in myelin diseases, we recently examined the human SVZ in post-mortem MS brains. The human SVZ is characterized by a ribbon of SVZ astrocytes lining the ependymal border of the lateral ventricles and which behave as multipotential progenitors in vitro. We showed that cellular density and proliferation were enhanced in MS SVZ compared to non-neurological controls. This high cellular density was correlated with the increased number of progenitor cells in MS SVZ, as well as in sub-ventricular lesions. Interestingly, some of these progenitors expressed transcription factors involved in oligodendrogenesis, such as Sox9, Olig2 and Sox10. These data indicate that gliogenesis occurs also in MS SVZ and suggest the recruitment of SVZ-derived oligodendrocyte precursors to peri-ventricular demyelinated lesions. Further investigation of adult neural stem cells and their progenitors in the brain of rodents and non-human primates should help to gain insights in their process of activation in response to demyelination and their role in myelin repair.
Nait-Oumesmar
B
B
INSERM U546, 75013 Paris, France.
Picard-Riéra
Nathalie
N
Kerninon
Christophe
C
Baron-Van Evercooren
A
A
D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D020547:Lateral Ventricles / Q000473:pathology*; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000473:pathology*