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Updated: Oct 21, 2025

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Cannabinoid receptor 2 is necessary to induce toll-like receptor-mediated microglial activation
Nico Reusch1,2, Kishore Aravind Ravichandran3, Bolanle Fatimat Olabiyi3
1Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Abstract:
The tight regulation of microglia activity is key for precise responses to potential threats, while uncontrolled and exacerbated microglial activity is neurotoxic. Microglial toll-like receptors (TLRs) are indispensable for sensing different types of assaults and triggering an innate immune response. Cannabinoid receptor 2 (CB2) signaling is a key pathway to control microglial homeostasis and activation, and its activation is connected to changes in microglial activity. We aimed to investigate how CB2 signaling impacts TLR-mediated microglial activation. Here, we demonstrate that deletion of CB2 causes a dampened transcriptional response to prototypic TLR ligands in microglia. Loss of CB2 results in distinct microglial gene expression profiles, morphology, and activation. We show that the CB2-mediated attenuation of TLR-induced microglial activation is mainly p38 MAPK-dependent. Taken together, we demonstrate that CB2 expression and signaling are necessary to fine-tune TLR-induced activation programs in microglia.
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