Tumor necrosis factor (TNF) and its receptors TNFR1 and TNFR2 have pleiotropic effects in neurodegenerative disorders. For example, while TNFR1 mediates neurodegenerative effects in multiple sclerosis, TNFR2 is protective and contributes to remyelination. The exact mode of TNFR2 action, however, is poorly understood. Here, we show that TNFR2-mediated activation of the PI3K-PKB/Akt pathway in pr...

Long non-coding RNAs (lncRNAs) have been implicated in numerous developmental processes. In a technical and bioinformatics tour-de-force, He et al. (2017) provide critical insight into the dynamics of lncRNA expression, function, and mechanism during oligodendrocyte development and after injury.

Recent evidence from studies mapping the expression of putative oligodendrocyte progenitor specific mRNAs has suggested that oligodendrocyte progenitors arise during embryogenesis, in specific foci of the neuroectoderm. In order to test this hypothesis, we have assayed different regions of the embryonic central nervous system for their ability to generate oligodendrocytes following transplantat...

BACKGROUND Neurodevelopmental delays in motor skills and white matter (WM) injury have been documented in congenital heart disease and after pediatric cardiac surgery. The lack of a suitable animal model has hampered our understanding of the cellular mechanisms underlying WM injury in these patients. Our aim is to identify an optimal surgical strategy for WM protection to reduce neurological in...

Serotonin/norepinephrine reuptake inhibitors antidepressants exert their effects by increasing serotonin and norepinephrine in the synaptic cleft. Studies show it takes 2-3 weeks for the mood-enhancing effects, which indicate other mechanisms may underlie their treatment effects. Here, we investigated the role of white matter in treatment and pathogenesis of depression using an unpredictable ch...

Prior studies support a role for mammalian target of rapamycin (mTOR) signaling in oligodendrocyte differentiation and myelination. Here we use Cre-recombinase driven by the CNP promoter to generate a mouse line with oligodendrocyte-specific knockdown of mTOR (mTOR cKO) in the CNS. We provide evidence that mTOR is necessary for proper oligodendrocyte differentiation and myelination in the spina...

Differentiation and maturation of oligodendroglial cells are postnatal processes that involve specific morphological changes correlated with the expression of stage-specific surface antigens and functional voltage-gated ion channels. A small fraction of oligodendrocyte progenitor cells (OPCs) generated during development are maintained in an immature and slowly proliferative or quiescent state ...

Elevated levels of extracellular glutamate cause excitotoxic oligodendrocyte cell death and contribute to progressive oligodendrocyte loss and demyelination in white matter disorders such as multiple sclerosis and periventricular leukomalacia. However, the mechanism by which glutamate homeostasis is altered in such conditions remains elusive. We show here that microglial cells, in their activat...

In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforminggrowth factor-β (Tgfβ) familyandsignal canonically via Smads1/5/8.Tgfβ ligandsandActivinscomprise theotherarmandsignal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgfβ li...

Oligodendrocytes are myelinating glial cells in the CNS and are essential for proper neuronal function. During development, oligodendrocyte progenitor cells (OPCs) are specified from the motor neuron precursor domain of the ventral spinal cord and differentiate into myelinating oligodendrocytes after migration to the white matter of the neural tube. Cell cycle control of OPCs influences the bal...