| First Author | Reyes JF | Year | 2014 |
| Journal | Glia | Volume | 62 |
| Issue | 3 | Pages | 387-98 |
| PubMed ID | 24382629 | Mgi Jnum | J:207504 |
| Mgi Id | MGI:5559000 | Doi | 10.1002/glia.22611 |
| Citation | Reyes JF, et al. (2014) Alpha-synuclein transfers from neurons to oligodendrocytes. Glia 62(3):387-98 |
| abstractText | The origin of alpha-synuclein (alpha-syn)-positive glial cytoplasmic inclusions found in oligodendrocytes in multiple system atrophy (MSA) is enigmatic, given the fact that oligodendrocytes do not express alpha-syn mRNA. Recently, neuron-to-neuron transfer of alpha-syn was suggested to contribute to the pathogenesis of Parkinson's disease. In this study, we explored whether a similar transfer of alpha-syn might occur from neurons to oligodendrocytes, which conceivably could explain how glial cytoplasmic inclusions are formed. We studied oligodendrocytes in vitro and in vivo and examined their ability to take up different alpha-syn assemblies. First, we treated oligodendrocytes with monomeric, oligomeric, and fibrillar forms of alpha-syn proteins and investigated whether alpha-syn uptake is dynamin-dependent. Second, we injected the same alpha-syn species into the mouse cortex to assess their uptake in vivo. Finally, we monitored the presence of human alpha-syn within rat oligodendroglial cells grafted in the striatum of hosts displaying Adeno-Associated Virus-mediated overexpression of human alpha-syn in the nigro-striatal pathway. Here, we show that oligodendrocytes take up recombinant alpha-syn monomers, oligomers and, to a lesser extent, fibrils in vitro in a concentration and time-dependent manner, and that this process is inhibited by dynasore. Further, we demonstrate in our injection model that oligodendrocytes also internalize alpha-syn in vivo. Finally, we provide the first direct evidence that alpha-syn can transfer to grafted oligodendroglial cells from host rat brain neurons overexpressing human alpha-syn. Our findings support the hypothesis of a neuron-to-oligodendrocyte transfer of alpha-syn, a mechanism that may play a crucial role in the progression and pathogenesis of MSA. |
