Amyloidogenic ?-synuclein seeds do not invariably induce rapid, widespread pathology in mice.

ABSTRACT: In order to further evaluate the parameters whereby intracerebral administration of recombinant ?-synuclein (?S) induces pathological phenotypes in mice, we conducted a series of studies where ?S fibrils were injected into the brains of M83 (A53T) and M47 (E46K) ?S transgenic (Tg) mice, and non-transgenic (nTg) mice. Using multiple markers to assess ?S inclusion formation, we find that injected fibrillar human ?S induced widespread cerebral ?S inclusion formation in the M83 Tg mice, but in both nTg and M47 Tg mice, induced ?S inclusion pathology is largely restricted to the site of injection. Furthermore, mouse ?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 ?S pathology within white matter tracts, and we attribute previous reports of white matter tract spreading to cross-reactivity of the ?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 ?S, there are significant barriers in mice to widespread induction of ?S pathology following intracerebral administration of amyloidogenic ?S.

SUBMITTER: Sacino AN 

PROVIDER: S-EPMC4869357 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature