| First Author | Sacino AN | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 37 | Pages | 12368-78 |
| PubMed ID | 25209277 | Mgi Jnum | J:310696 |
| Mgi Id | MGI:6763783 | Doi | 10.1523/JNEUROSCI.2102-14.2014 |
| Citation | Sacino AN, et al. (2014) Brain injection of alpha-synuclein induces multiple proteinopathies, gliosis, and a neuronal injury marker. J Neurosci 34(37):12368-78 |
| abstractText | Intracerebral injection of amyloidogenic alpha-synuclein (alphaS) has been shown to induce alphaS pathology in the CNS of nontransgenic mice and alphaS transgenic mice, albeit with varying efficiencies. In this study, using wild-type human alphaS transgenic mice (line M20), we demonstrate that intracerebral injection of recombinant amyloidogenic or soluble alphaS induces extensive alphaS intracellular inclusion pathology that is associated with robust gliosis. Near the injection site, a significant portion of alphaS inclusions are detected in neurons but also in astrocytes and microglia. Aberrant induction of expression of the intermediate filament protein peripherin, which is associated with CNS neuronal injury, was also observed predominantly near the site of injection. In addition, many pSer129 alphaS-induced inclusions colocalize with the low-molecular-mass neurofilament subunit (NFL) or peripherin staining. alphaS inclusion pathology was also induced in brain regions distal from the injection site, predominantly in neurons. Unexpectedly, we also find prominent p62-immunoreactive, alphaS-, NFL-, and peripherin-negative inclusions. These findings provide evidence that exogenous alphaS challenge induces alphaS pathology but also results in the following: (1) a broader disruption of proteostasis; (2) glial activation; and (3) a marker of a neuronal injury response. Such data suggest that induction of alphaS pathology after exogenous seeding may involve multiple interdependent mechanisms. |
