Neural progenitor cells (NPCs) are capable of differentiating into oligodendrocytes, cells capable of remyelinating MS lesions. Brain-derived neurotrophic factor (BDNF) and platelet-derived growth factor AA (PDGF-AA) are two neurotrophic factors that may stimulate NPC differentiation and likely play a role in MS pathogenesis. While several studies have demonstrated the proliferative and protective capabilities of these factors, an understanding of their direct actions on NPCs is required in order to better understand how these factors can be used therapeutically to promote remyelination. We investigate how BDNF and PDGF-AA influence postnatal mNPC physiology. We identify that neither factor promotes NPC proliferation or protects against apoptosis, and that both factors promote NPC differentiation into the neuronal and oligo-lineage in a time-dependent fashion. PDGF-AA specifically induces oligo-lineage differentiation. These findings highlight the importance of neurotrophic factors in stimulating NPC differentiation, and offer insight into how to develop neurotrophic factor replacement therapies to achieve the goal of remyelination. Multiple sclerosis (MS) manifests as inflammatory, demyelinating central nervous system (CNS) lesions. The harsh lesion microenvironment does not support the successful remyelination of damaged axons. Acute lesions that are capable of limited remyelination ultimately progress into chronic lesions that are incapable of remyelination altogether.
Last date updated on September, 2020