2024-03-29T08:06:50Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1991322020-01-30T02:07:08Zcom_10261_54com_10261_1col_10261_307
Endocannabinoids drive the acquisition of an alternative phenotype in microglia
Mecha, Miriam
Feliú, Ana
Carrillo-Salinas, F. J.
Rueda-Zubiaurre, A.
Ortega-Gutiérrez, S.
García de Sola, R.
Guaza, Carmen
Ministerio de Economía y Competitividad (España)
Comunidad de Madrid
Red Española de Esclerosis Múltiple
Microglia
M2 polarization
AEA
2-AG
CB2 receptors
The ability of microglia to acquire diverse states of activation, or phenotypes, reflects different features that are determinant for their contribution to homeostasis in the adult CNS, and their activity in neuroinflammation, repair or immunomodulation. Despite the widely reported immunomodulatory effects of cannabinoids in both the peripheral immune system and the CNS, less is known about how the endocannabinoid signaling system (eCBSS) influence the microglial phenotype. The general aim of the present study was to investigate the role of endocannabinoids in microglia polarization by using microglia cell cultures. We show that alternative microglia (M2a) and acquired deactivated microglia (M2c) exhibit changes in the eCB machinery that favor the selective synthesis of 2-AG and AEA, respectively. Once released, these eCBs might be able to act through CB1 and/or CB2 receptors in order to influence the acquisition of an M2 phenotype. We present three lines of evidence that the eCBSS is critical for the acquisition of the M2 phenotype: (i) M2 polarization occurs on exposure to the two main endocannabinoids 2-AG and AEA in microglia cultures; (ii) cannabinoid receptor antagonists block M2 polarization; and (iii) M2 polarization is dampened in microglia from CB2 receptor knockout mice. Taken together, these results indicate the interest of eCBSS for the regulation of microglial activation in normal and pathological conditions.
2020-01-29T08:41:24Z
2020-01-29T08:41:24Z
2015-10
2020-01-29T08:41:24Z
artículo
Brain, Behavior, and Immunity 49: 233-245 (2015)
0889-1591
http://hdl.handle.net/10261/199132
10.1016/j.bbi.2015.06.002
1090-2139
http://dx.doi.org/10.13039/501100007747
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/100012818
http://dx.doi.org/10.1016/j.bbi.2015.06.002
Sí
S2010/BMD-2308
S2010/BMD-2353
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-42784-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-48271
closedAccess
Elsevier