Adult-born SVZ progenitors receive transient synapses during remyelination in corpus callosum

ArticleinNature Neuroscience 13(3):287-9 · February 2010with16 Reads
DOI: 10.1038/nn.2500 · Source: PubMed
We found that demyelinated axons formed functional glutamatergic synapses onto adult-born NG2(+) oligodendrocyte progenitor cells (OPCs) migrating from the subventricular zone after focal demyelination of adult mice corpus callosum. This glutamatergic input was substantially reduced compared with endogenous callosal OPCs 1 week after lesion and was lost on differentiation into oligodendrocytes. Therefore, axon-oligodendrocyte progenitor synapse formation is a transient and regulated step that occurs during remyelination of callosal axons.
    • "Remyelination is carried out by OPCs that migrate to the site of damage, proliferate, differentiate and wrap their processes around the demyelinated axons to form a new myelin sheath (see reviews in this issue by Chamberlain et al., 2016; Tognatta and Miller, 2016). It has been shown recently that demyelinated axons upregulate presynaptic proteins in the ethidium bromide lesion model in rats (Gautier et al., 2015), in lysolecithin lesions in mice (Etxeberria et al., 2010; Sahel et al., 2015) and in MS patients, and are able to form synapses with recruited OPCs (Gautier et al., 2015; Sahel et al., 2015). These OPCs express AMPA/kainate receptors and, at later stages, also NMDA receptors (Gautier et al., 2015). "
    [Show abstract] [Hide abstract] ABSTRACT: Myelin is essential for the mammalian brain to function efficiently. Whilst many factors have been associated with regulating the differentiation of oligodendroglia and myelination, glutamate signalling might be particularly important for learning-dependent myelination. The majority of myelinated projection neurons are glutamatergic. Oligodendrocyte precursor cells receive glutamatergic synaptic inputs from unmyelinated axons and oligodendrocyte lineage cells express glutamate receptors which enable them to monitor and respond to changes in neuronal activity. Yet, what role glutamate plays for oligodendroglia is not fully understood. Here, we review glutamate signalling and its effects on oligodendrocyte lineage cells, and myelination in health and disease. Furthermore, we discuss whether glutamate signalling between neurons and oligodendroglia might lay the foundation to activity-dependent white matter plasticity.
    Full-text · Article · Jun 2016
    • "The AMPA and NMDA receptors are expressed in mature oligodendrocyte somata and myelin, respectively [132, 140], and this has led to the hypothesis that communication between axons and myelin represents a new type of " axon-myelin synapse " [141] . After demyelination , the formation of neuron-NG2-glia synapses suggests that synaptic glutamate signalling is important for the early stages of remyelination [142]. Thus, myelination/remyelination is dependent on axonal activity and glutamatergic signalling even in adulthood [42]. "
    [Show abstract] [Hide abstract] ABSTRACT: Glial cells and their association with neurones are fundamental for brain function. The emergence of complex neurone-glial networks assures rapid information transfer, creating a sophisticated circuitry where both types of neural cells work in concert, serving different activities. All glial cells, represented by astrocytes, oligodendrocytes, microglia and NG2-glia, are essential for brain homeostasis and defence. Thus, glia are key not only for normal central nervous system (CNS) function, but also to its dysfunction, being directly associated with all forms of neuropathological processes. Therefore, the progression and outcome of neurological and neurodegenerative diseases depend on glial reactions. In this review, we provide a concise account of recent data obtained from both human material and animal models demonstrating the pathological involvement of glia in neurodegenerative processes, including Alzheimer's disease (AD), as well as physiological ageing.
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    • "To investigate whether Stat3 plays a role in remyelination after injury , we employed a well-established lysolecithin (LPC)-induced demyelination/remyelination model. In this model, chemically induced focal demyelination is followed by a robust, spontaneous regenerative process , comprising OPC migration and proliferation into the lesion (3– 7 days post lesion (dpl)), differentiation into myelin-producing OLs (7–14 dpl) and active remyelination (14–21 dpl) (Etxeberria et al., 2010; Huang et al., 2011; Wegener et al., 2015). CNTF expression has been previously shown to be upregulated during the peak of demyelination (Vernerey et al., 2013) as well as during the remyelination phase ((Huang et al., 2011 ). "
    [Show abstract] [Hide abstract] ABSTRACT: Multiple sclerosis is the most prevalent demyelinating disease of the central nervous system (CNS) and is histologically characterized by perivascular demyelination as well as neurodegeneration. While the degree of axonal damage is correlated with clinical disability, it is believed that remyelination can protect axons from degeneration and slow disease progression. Therefore, understanding the intricacies associated with myelination and remyelination may lead to therapeutics that can enhance the remyelination process and slow axon degeneration and loss of function. Ciliary neurotrophic factor (CNTF) family cytokines such as leukemia inhibitory factor (LIF) and interleukin 11 (IL-11) are known to promote oligodendrocyte maturation and remyelination in experimental models of demyelination. Because CNTF family member binding to the gp130 receptor results in activation of the JAK2/Stat3 pathway we investigated the necessity of oligodendroglial Stat3 in transducing the signal required for myelination and remyelination. We found that Stat3 activation in the CNS coincides with myelination during development. Stimulation of oligodendrocyte precursor cells (OPCs) with CNTF or LIF promoted OPC survival and final differentiation, which was completely abolished by pharmacologic blockade of Stat3 activation with JAK2 inhibitor. Similarly, genetic ablation of Stat3 in oligodendrocyte lineage cells prevented CNTF-induced OPC differentiation in culture. In vivo, while oligodendroglial Stat3 signaling appears to be dispensable for developmental CNS myelination, it is required for oligodendrocyte regeneration and efficient remyelination after toxin-induced focal demyelination in the adult brain. Our data suggest a critical function for oligodendroglial Stat3 signaling in myelin repair.
    Full-text · Article · Apr 2016
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