科研之友
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摘要
In order to further evaluate the parameters whereby intracerebral administration of recombinant alpha-synuclein (alpha S) induces pathological phenotypes in mice, we conducted a series of studies where alpha S fibrils were injected into the brains of M83 (A53T) and M47 (E46K) alpha S transgenic (Tg) mice, and non-transgenic (nTg) mice. Using multiple markers to assess alpha S inclusion formation, we find that injected fibrillar human alpha S induced widespread cerebral alpha S inclusion formation in the M83 Tg mice, but in both nTg and M47 Tg mice, induced alpha S inclusion pathology is largely restricted to the site of injection. Furthermore, mouse alpha S fibrils injected into nTg mice brains also resulted in inclusion pathology restricted to the site of injection with no evidence for spread. We find no compelling evidence for extensive spread of alpha S pathology within white matter tracts, and we attribute previous reports of white matter tract spreading to cross-reactivity of the alpha S pSer129/81A antibody with phosphorylated neurofilament subunit L. These studies suggest that, with the exception of the M83 Tg mice which appear to be uniquely susceptible to induction of inclusion pathology by exogenous forms of alpha S, there are significant barriers in mice to widespread induction of alpha S pathology following intracerebral administration of amyloidogenic alpha S.
- 出版日期2014-5
