Dataset Information


Opposite roles for astrocytes in developmental myelination and early myelin repair

ABSTRACT: Understanding the regulation of oligodendrocyte development and myelination in the central nervous system (CNS) is essential, not only to facilitate myelin repair but also to define the role of oligodendrocytes in maintaining axonal integrity. In vitro studies have implicated astrocytes in influencing multiple aspects of oligodendrocytes and their precursors, however the in vivo role of astrocytes in myelination and myelin repair remain poorly defined. We show that astrocyte ablation during postnatal spinal cord development resulted in a concomitant delay in myelination, demonstrating a critical role for astrocytes in promoting developmental myelination. By contrast, in the adult CNS, localized ablation of astrocytes 2 days after a demyelinating insult resulted in increased numbers of oligodendrocytes and accelerated remyelination in both the spinal cord and the corpus callosum. Microarray analysis reveals astrocytic NF-kB signaling pathway as a major contributor to pathological events occurring after demyelination. We suggest that the localized functions of astrocytes are fundamentally different during developmental myelination and myelin repair. Astrocytes are critical for developmental myelination, however in a demyelinating environment they are detrimental to myelin repair. Overall design: Due to potentially conflicting roles for astrocytes in demyelination and myelin repair, it becomes challenging to target astrocytes for therapeutic intervention in demyelinating diseases such as MS. Not only is there uncertainty regarding the roles of astrocytes in demyelination, but their roles in developmental myelination in-vivo remain ill defined, with much of our understanding coming from in vitro studies . In the current study, we developed a transgenic strategy that allows for the selective elimination of non-proliferative GFAP+ astrocytes through the targeted induction of physiological apoptosis that allows detailed loss of function analysis.

INSTRUMENT(S): [MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version]

SUBMITTER: Robert H Miller  

PROVIDER: GSE60276 | GEO | 2017-08-01



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