| First Author | Harms AS | Year | 2018 |
| Journal | Exp Neurol | Volume | 300 |
| Pages | 179-187 | PubMed ID | 29155051 |
| Mgi Jnum | J:261154 | Mgi Id | MGI:6152980 |
| Doi | 10.1016/j.expneurol.2017.11.010 | Citation | Harms AS, et al. (2018) Peripheral monocyte entry is required for alpha-Synuclein induced inflammation and Neurodegeneration in a model of Parkinson disease. Exp Neurol 300:179-187 |
| abstractText | Accumulation of alpha-synuclein (alpha-syn) in the central nervous system (CNS) is a core feature of Parkinson disease (PD) that leads to activation of the innate immune system, production of inflammatory cytokines and chemokines, and subsequent neurodegeneration. Here, we used heterozygous reporter knock-in mice in which the first exons of the fractalkine receptor (CX3CR1) and of the C-C chemokine receptor type 2 (CCR2) are replaced with fluorescent reporters to study the role of resident microglia (CX3CR1+) and infiltrating peripheral monocytes (CCR2+), respectively, in the CNS. We used an alpha-syn mouse model induced by viral over-expression of alpha-syn. We find that in vivo, expression of full-length human alpha-syn induces robust infiltration of pro-inflammatory CCR2+ peripheral monocytes into the substantia nigra. Genetic deletion of CCR2 prevents alpha-syn induced monocyte entry, attenuates MHCII expression and blocks the subsequent degeneration of dopaminergic neurons. These results demonstrate that extravasation of pro-inflammatory peripheral monocytes into the CNS plays a key role in neurodegeneration in this model of PD synucleinopathy, and suggest that peripheral monocytes may be a target of neuroprotective therapies for human PD. |
