Frühbeis C, Fröhlich D, Krämer-Albers EM. Emerging roles of exosomes in neuron-glia communication.Front Physiol. 2012 Apr 30;3:119.
Brain function depends on coordinated interactions between neurons and glial cells. Recent evidence indicates that these cells release endosome-derived microvesicles termed exosomes, which are 50-100 nm in size and carry specific protein and RNA cargo. Exosomes can interact with neighbouring cells raising the concept that exosomes may mediate signalling between brain cells and facilitate the delivery of bioactive molecules. Oligodendrocytes myelinate axons and furthermore maintain axonal integrity by an yet uncharacterized pathway of trophic support. Here, we highlight the role of exosomes in nervous system cell communication with particular focus on exosomes released by oligodendrocytes and their potential implications in axon-glia interaction and myelin disease, such as multiple sclerosis. These secreted vesicles may contribute to eliminate overproduced myelin membrane or to transfer antigens facilitating immune surveillance of the brain. Furthermore, there is emerging evidence that exosomes participate in axon-glia communication.
Pusic AD, Pusic KM, Clayton BL, Kraig RP. IFNγ-stimulated dendritic cell exosomes as a potential therapeutic for remyelination. J Neuroimmunol. 2014 Jan 15;266(1-2):12-23.
Dendritic cells (DCs) release exosomes with different characteristics based on stimulus. Here, we showed that DC cultures stimulated with low-level IFNγ (gamma interferon and immune stimulator) released exosomes (IFNγ-DC-Exos) that contained microRNA species that can increase baseline myelination, reduce oxidative stress, and improve remyelination following chemical (lysolecithin)-induced demyelination. Furthermore, nasally administered IFNγ-DC-Exos increased CNS myelination in vivo. IFNγ-DC-Exos were preferentially taken up by oligodendrocytes, suggesting that they directly impact oligodendrocytes to increase myelination. Thus, our results show great potential for use of these IFNγ-DC-Exos as a therapeutic to promote remyelination in multiple sclerosis and dysmyelinating syndromes.
Pusic AD, Kraig RP Youth and environmental enrichment generate serum exosomes containing miR-219 that promote CNS myelination.Glia. 2014; 62(2):284-99.
Although commonly considered a disease of white matter, gray matter demyelination is increasingly recognized as an important component of multiple sclerosis (MS) pathogenesis, particularly in the secondary progressive disease phase. Extent of damage to gray matter is strongly correlated to decline in memory and cognitive dysfunction in MS patients. Aging likewise occurs with cognitive decline from myelin loss, and age-associated failure to remyelinate significantly contributes to MS progression. However, recent evidence demonstrates that parabiotic exposure of aged animals to a youthful systemic milieu can promote oligodendrocyte precursor cell (OPC) differentiation and improve remyelination. In the current study, we focus on this potential for stimulating remyelination, and show it involves serum (blood fluid) exosomes that increase OPCs and their differentiation into mature myelin-producing cells-both under control conditions and after acute demyelination. Environmental enrichment (EE) of aging animals produced exosomesthat mimicked this promyelinating effect. Additionally, stimulating OPC differentiation via exosomes derived from environmentally enriched animals is unlikely to deplete progenitors, as EE itself promotes proliferation of neural stem cells. We found that both young and EE serum-derived exosomeswere enriched in miR-219, which is necessary and sufficient for production of myelinating oligodendrocytes by reducing the expression of inhibitory regulators of differentiation. Accordingly, protein transcript levels of these miR-219 target mRNAs decreased following exosome application to slice cultures. Finally, nasal administration of exosomes to aging rats also enhanced myelination. Thus, peripheral circulating cells in young or environmentally enriched animals produce exosomes that may be a useful therapy for remyelination.
we have done alot of posts of microRNAs