Cannabidiol-induced apoptosis in murine microglial cells through lipid raft

Cannabidiol (CBD), the major nonpsychotropic phytocannabinoid, induces apoptosis in both immortalized and primary lymphocytes and monocytes. However, contrasting effects of CBD on the apoptosis between normal and immortalized glial cells have been reported. This study investigated the proapoptotic e...

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Published in:Glia 2012-07, Vol.60 (7), p.1182-1190
Main Authors: Wu, Hsin-Ying, Goble, Kathleen, Mecha, Miriam, Wang, Chia-Chi, Huang, Chung-Hsiung, Guaza, Carmen, Jan, Tong-Rong
Format: Article
Language:English
Subjects:
Animals
apoptosis
Apoptosis - drug effects
cannabidiol
Cannabidiol - pharmacology
Caspases - metabolism
Caveolin 1 - metabolism
caveolin-1
Dose-Response Relationship, Drug
GM1
lipid raft
Membrane Microdomains - drug effects
Membrane Microdomains - metabolism
Mice
microglia
Microglia - drug effects
Microglia - metabolism
Receptor, Cannabinoid, CB1 - metabolism
Receptor, Cannabinoid, CB2 - metabolism
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Summary:Cannabidiol (CBD), the major nonpsychotropic phytocannabinoid, induces apoptosis in both immortalized and primary lymphocytes and monocytes. However, contrasting effects of CBD on the apoptosis between normal and immortalized glial cells have been reported. This study investigated the proapoptotic effect of CBD on primary microglial cells. Treatment of murine primary microglial cultures with CBD resulted in a time‐ and concentration‐dependent induction of apoptosis, as shown by increase in hypodiploid cells and DNA strand breaks, and marked activation of both caspase‐8 and −9. Mechanistic studies revealed that antioxidants, including N‐acetyl‐L‐cysteine and glutathione, the G protein‐coupled receptor 55 agonist abnormal‐CBD and specific antagonists for vanilloid, and CB1 and CB2 cannabinoid receptors did not counteract the apoptosis induced by CBD. In contrast, methyl‐β‐cyclodextrin (MCD), a lipid raft disruptor, potently attenuated CBD‐induced microglial apoptosis and caspase activation. Furthermore, CBD induced lipid raft coalescence and augmented the expression of GM1 ganglioside and caveolin‐1, all of which were attenuated by MCD. Taken together, these results suggest that CBD induces a marked proapoptotic effect in primary microglia through lipid raft coalescence and elevated expression of GM1 ganglioside and caveolin‐1. © 2012 Wiley Periodicals, Inc.
ISSN:0894-1491
1098-1136
DOI:10.1002/glia.22345