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Long-term polarization of microglia upon α-synuclein overexpression in nonhuman primates

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Author

  • P. Barkholt
  • V. Sanchez-Guajardo
  • Deniz Kirik
  • M. Romero-Ramos

Summary, in English

We have previously shown that persistent a-synuclein 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) alpha-synuclein. However, A53T alpha-synuclein overexpression induced neurodegeneration that resulted in nigral dopaminergic cell death. Here, we analyze the microglia population in the midbrain of these animals by stereological quantification of lba1 + cells. Our data here show that monkeys overexpressing A53T alpha-synuclein showed a long-term increase in microglia presenting macrophagic morphology. However, wt alpha-synuclein overexpression, despite the absence 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 differs depending on the type of alpha-synuclein (wt/A53T) and/or whether alpha-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 alpha-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) alpha-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. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Publishing year

2012

Language

English

Pages

85-96

Publication/Series

Neuroscience

Volume

208

Document type

Journal article

Publisher

Elsevier

Topic

  • Neurosciences

Keywords

  • Parkinson's disease
  • primate
  • microglia
  • alpha-synuclein
  • lba-1
  • neuroinflammation

Status

Published

Research group

  • Brain Repair and Imaging in Neural Systems (BRAINS)

ISBN/ISSN/Other

  • ISSN: 1873-7544