Cellular and Molecular Neurobiology

, Volume 37, Issue 3, pp 461–473 | Cite as

Regulation of Microglial Phagocytosis by RhoA/ROCK-Inhibiting Drugs

Original Research


Inflammation within the central nervous system (CNS) is a major component of many neurodegenerative diseases. The underlying mechanisms of neuronal loss are not fully understood, but the activation of CNS resident phagocytic microglia seems to be a significant element contributing to neurodegeneration. At the onset of inflammation, high levels of microglial phagocytosis may serve as an essential prerequisite for creating a favorable environment for neuronal regeneration. However, the excessive and long-lasting activation of microglia and the augmented engulfment of neurons have been suggested to eventually govern widespread neurodegeneration. Here, we investigated in a functional assay of acute inflammation how the small GTPase RhoA and its main target the Rho kinase (ROCK) influence microglial phagocytosis of neuronal debris. Using BV-2 microglia and human NT2 model neurons, we demonstrate that the pain reliever Ibuprofen decreases RhoA activation and microglial phagocytosis of neuronal cell fragments. Inhibition of the downstream effector ROCK with the small-molecule agents Y-27632 and Fasudil reduces the engulfment of neuronal debris and attenuates the production of the inflammatory mediator nitric oxide during stimulation with lipopolysaccharide. Our results support a therapeutic potential for RhoA/ROCK-inhibiting agents as an effective treatment of excessive inflammation and the resulting progression of microglia-mediated neurodegeneration in the CNS.


RhoA Y-27632 Fasudil BV-2 microglia Human NT2 neurons 



This work was supported by a grant of the German Research Foundation: BI 262/16-2. The authors would like to thank Saime Tan for generating the human NT2 neurons and our colleagues from the Forschergruppe 1103 for their contributions regarding glial culture. We are grateful to Frank Roloff and Michael Stern for helpful discussions.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Division of Cell BiologyUniversity of Veterinary Medicine HannoverHannoverGermany
  2. 2.Center for Systems NeuroscienceHannoverGermany

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