Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The endocannabinoid anandamide (AEA) is released by macrophages and microglia on pathological neuroinflammatory conditions such as multiple sclerosis (MS). CD200 is a membrane glycoprotein expressed in neurons that suppresses immune activity via its receptor (CD200R) mainly located in macrophages/microglia. CD200-CD200R interactions contribute to the brain immune privileged status. In this study, we show that AEA protects neurons from microglia-induced neurotoxicity via CD200-CD200R interaction. AEA increases the expression of CD200R1 in LPS/IFN-γ activated microglia through the activation of CB(2) receptors. The neuroprotective effect of AEA disappears when microglial cells derive from CD200R1(-/-) mice. We also show that engagement of CD200R1 by CD200Fc decreased the production of the proinflammatory cytokines IL-1β and IL-6, but increased IL-10 in activated microglia. In the chronic phases of Theiler's virus-induced demyelinating disease (TMEV-IDD) the expression of CD200 and CD200R1 was reduced in the spinal cord. AEA-treated animals up-regulated the expression of CD200 and CD200R1, restoring levels found in sham animals together with increased expression of IL-10 and reduced expression of IL-1β and IL-6. Treated animals also improved their motor behavior. Because AEA up-regulated the expression of CD200R1 in microglia, but failed to enhance CD200 in neurons we suggest that AEA-induced up-regulation of CD200 in TMEV-IDD is likely due to IL-10 as this cytokine increases CD200 in neurons. Our findings provide a new mechanism of action of AEA to limit immune response in the inflamed brain.

Original publication

DOI

10.1002/glia.22366

Type

Journal article

Journal

Glia

Publication Date

09/2012

Volume

60

Pages

1437 - 1450

Addresses

Department of Functional and Systems Neurobiology, Neuroimmunology Group, Instituto Cajal, CSIC, Madrid, Spain.

Keywords

Brain, Microglia, Neurons, Cells, Cultured, Animals, Mice, Inflammation, Arachidonic Acids, Receptors, Cell Surface, Neuroprotective Agents, Antigens, CD, Interleukin-6, Antigens, Surface, Endocannabinoids, Polyunsaturated Alkamides, Interleukin-1beta, Orexin Receptors