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Author Notes:

Stefka Gyoneva, Department of Pharmacology, Rollins Research Center Rm 5062, 1510 Clifton Rd. NE, Atlanta, GA 30322; Tel.: (404) 727-1375, Fax: (404) 727-0365; stefka.gyoneva@gmail.com..

Thanks are also due to Susan Jenkins for technical assistance.

Finally, we thank Dr. Malu Tansey for helpful discussions and suggestions while preparing the manuscript; and Dr. David Weinshenker for providing TH-GFP mice to us.

The authors declare no competing financial interests.


Research Funding:

Funding was provided by NINDS NRSA (F31NS076215, S.G.); NIEHS Toxicology institutional training grant (T32ES12870, S.G.); NIH Pharmacological Sciences institutional training grant (T32GM008602, S.G.); a pilot grant from the Emory University Udall Center for Parkinson’s Disease Research (NIH/NINDS P50-NS071669, S.F.T); the Alzheimer’s Disease Research Center (NIHP50 AG025688, S.F.T.); the Yerkes Primate Center NIH base grant (RR00165, Y.S.); and the Emory University Integrated Cellular Imaging Microscopy Core.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • Parkinson's disease
  • Microglia
  • Adenosine A(2A) receptor
  • Preladenant
  • Acute brain slice
  • Imaging
  • Neuroinflammation

Adenosine A(2A) receptor antagonism reverses inflammation-induced impairment of microglial process extension in a model of Parkinson's disease

Journal Title:

Neurobiology of Disease


Volume 67


, Pages 191-202

Type of Work:

Article | Post-print: After Peer Review


Microglia, the immune cells of the central nervous system, constantly survey the parenchyma in the healthy brain to maintain homeostasis. When a disturbance, such as cell death, results in ATP release in vivo, microglial processes respond by utilizing P2Y12 purinergic receptors to trigger extension toward the site of damage. Processes ultimately surround the injury site, preventing the spread of harmful cellular constituents and assisting with tissue repair. In contrast to the healthy brain, many neurodegenerative diseases, including Parkinson's disease, are characterized by the presence of neuroinflammation. Yet, the ability of microglia to respond to tissue damage under pro-inflammatory conditions has not been well studied. To assess the ability of microglia to respond to tissue injury and localized cell death in the context of Parkinson's disease, we performed confocal imaging of acute brain slices from mice with microglia-specific green fluorescent protein expression. Microglia in coronal slices containing the substantia nigra extend processes toward a mechanical injury in a P2Y12 receptor-dependent manner. However, microglia in mice treated for 5days with 20mg/kg/day 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) show significantly reduced process displacement toward the injury compared to microglia in control animals. Pre-treatment of slices from MPTP-injected mice with the A2A receptor-selective antagonist preladenant restores the ability of activated microglia to respond to tissue damage. These data support the hypothesis that chronic inflammation impedes microglial motility in response to further injury, such as cell death, and suggest that some aspects of the neuroprotection observed with adenosine A2A receptor antagonists may involve direct or indirect actions at microglia.

Copyright information:

© 2014 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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