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1 Department of Biomedicine - Forskning og uddannelse, Vest, Department of Biomedicine, Health, Aarhus University 2 Department of Biomedicine - Forskning og uddannelse, Øst, Department of Biomedicine, Health, Aarhus University 3 unknown 4 Department of Biomedicine - Forskning og uddannelse, Vest, Department of Biomedicine, Health, Aarhus University 5 Department of Biomedicine - Forskning og uddannelse, Øst, Department of Biomedicine, Health, Aarhus University
We have previously shown that persistent ﰇ-sy- nuclein overexpression in ventral midbrain of marmoset leads to a distinctive neurodegenerative process and motor defects. The neurodegeneration was confined to caudate putamen dopaminergic fibers in animals overexpressing wild-type (wt) ﰇ-synuclein. However, A53T ﰇ-synuclein over- expression induced neurodegeneration that resulted in nigral dopaminergic cell death. Here, we analyze the microglia po- pulation in the midbrain of these animals by stereological quantification of Iba1ﰉ cells. Our data here show that mon- keys overexpressing A53T ﰇ-synuclein showed a long-term increase in microglia presenting macrophagic morphology. However, wt ﰇ-synuclein overexpression, despite the ab- sence of dopaminergic cell death, resulted in a permanent robust increase of the microglia population characterized by a range of distinct morphological types that persisted after 1 year. These results confirm that the microglial response dif- fers depending on the type of ﰇ-synuclein (wt/A53T) and/or whether ﰇ-synuclein expression results in cell death or not, suggesting that microglia may play different roles during disease progression. Furthermore, the microglial response is modulated by events related to ﰇ-synuclein expression in substantia nigra and persists in the long term. The data presented here is in agreement with that previously observed in a recombinant adeno-associated virus (rAAV) ﰇ-synuclein rat model, thereby validating both the findings and the model, and highlighting the translational potential of the rodent model to higher species closer to humans. © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
Neuroscience, 2012, Vol 208, p. 85-96
Parkinson’s disease, primate, microglia, -sy- nuclein, Iba-1, neuroinflammation
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