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The non-psychoactive plant cannabinoid, cannabidiol affects cholesterol metabolism-related genes in microglial cells.
Cell Mol Neurobiol. 2011 Aug; 31(6):921-30.CM

Abstract

Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that is clinically used in a 1:1 mixture with the psychoactive cannabinoid Δ(9)-tetrahydrocannabinol (THC) for the treatment of neuropathic pain and spasticity in multiple sclerosis. Our group previously reported that CBD exerts anti-inflammatory effects on microglial cells. In addition, we found that CBD treatment increases the accumulation of the endocannabinoid N-arachidonoyl ethanolamine (AEA), thus enhancing endocannabinoid signaling. Here we proceeded to investigate the effects of CBD on the modulation of lipid-related genes in microglial cells. Cell viability was tested using FACS analysis, AEA levels were measured using LC/MS/MS, gene array analysis was validated with real-time qPCR, and cytokine release was measured using ELISA. We report that CBD significantly upregulated the mRNAs of the enzymes sterol-O-acyl transferase (Soat2), which synthesizes cholesteryl esters, and of sterol 27-hydroxylase (Cyp27a1). In addition, CBD increased the mRNA of the lipid droplet-associated protein, perilipin2 (Plin2). Moreover, we found that pretreatment of the cells with the cholesterol chelating agent, methyl-β-cyclodextrin (MBCD), reversed the CBD-induced increase in Soat2 mRNA but not in Plin2 mRNA. Incubation with AEA increased the level of Plin2, but not of Soat2 mRNA. Furthermore, MBCD treatment did not affect the reduction by CBD of the LPS-induced release of the proinflammatory cytokine IL-1β. CBD treatment modulates cholesterol homeostasis in microglial cells, and pretreatment with MBCD reverses this effect without interfering with CBD's anti-inflammatory effects. The effects of the CBD-induced increase in AEA accumulation on lipid-gene expression are discussed.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Rimmerman N
The Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel. neta.rimmerman@gmail.com
Juknat A
No affiliation info available
Kozela E
No affiliation info available
Levy R
No affiliation info available
Bradshaw HB
No affiliation info available
Vogel Z
No affiliation info available

MeSH

AnimalsArachidonic AcidsCannabidiolCell DeathCell LineCholesterolCulture Media, Serum-FreeDronabinolEndocannabinoidsGene Expression RegulationInterleukin-1betaLipid MetabolismLipopolysaccharidesMiceMicrogliaOligonucleotide Array Sequence AnalysisPlantsRNA, MessengerTime Factorsbeta-Cyclodextrins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21533611

Citation

Rimmerman, Neta, et al. "The Non-psychoactive Plant Cannabinoid, Cannabidiol Affects Cholesterol Metabolism-related Genes in Microglial Cells." Cellular and Molecular Neurobiology, vol. 31, no. 6, 2011, pp. 921-30.
Rimmerman N, Juknat A, Kozela E, et al. The non-psychoactive plant cannabinoid, cannabidiol affects cholesterol metabolism-related genes in microglial cells. Cell Mol Neurobiol. 2011;31(6):921-30.
Rimmerman, N., Juknat, A., Kozela, E., Levy, R., Bradshaw, H. B., & Vogel, Z. (2011). The non-psychoactive plant cannabinoid, cannabidiol affects cholesterol metabolism-related genes in microglial cells. Cellular and Molecular Neurobiology, 31(6), 921-30. https://doi.org/10.1007/s10571-011-9692-3
Rimmerman N, et al. The Non-psychoactive Plant Cannabinoid, Cannabidiol Affects Cholesterol Metabolism-related Genes in Microglial Cells. Cell Mol Neurobiol. 2011;31(6):921-30. PubMed PMID: 21533611.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The non-psychoactive plant cannabinoid, cannabidiol affects cholesterol metabolism-related genes in microglial cells. AU - Rimmerman,Neta, AU - Juknat,Ana, AU - Kozela,Ewa, AU - Levy,Rivka, AU - Bradshaw,Heather B, AU - Vogel,Zvi, Y1 - 2011/04/30/ PY - 2011/02/27/received PY - 2011/04/08/accepted PY - 2011/5/3/entrez PY - 2011/5/3/pubmed PY - 2011/12/13/medline SP - 921 EP - 30 JF - Cellular and molecular neurobiology JO - Cell Mol Neurobiol VL - 31 IS - 6 N2 - Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that is clinically used in a 1:1 mixture with the psychoactive cannabinoid Δ(9)-tetrahydrocannabinol (THC) for the treatment of neuropathic pain and spasticity in multiple sclerosis. Our group previously reported that CBD exerts anti-inflammatory effects on microglial cells. In addition, we found that CBD treatment increases the accumulation of the endocannabinoid N-arachidonoyl ethanolamine (AEA), thus enhancing endocannabinoid signaling. Here we proceeded to investigate the effects of CBD on the modulation of lipid-related genes in microglial cells. Cell viability was tested using FACS analysis, AEA levels were measured using LC/MS/MS, gene array analysis was validated with real-time qPCR, and cytokine release was measured using ELISA. We report that CBD significantly upregulated the mRNAs of the enzymes sterol-O-acyl transferase (Soat2), which synthesizes cholesteryl esters, and of sterol 27-hydroxylase (Cyp27a1). In addition, CBD increased the mRNA of the lipid droplet-associated protein, perilipin2 (Plin2). Moreover, we found that pretreatment of the cells with the cholesterol chelating agent, methyl-β-cyclodextrin (MBCD), reversed the CBD-induced increase in Soat2 mRNA but not in Plin2 mRNA. Incubation with AEA increased the level of Plin2, but not of Soat2 mRNA. Furthermore, MBCD treatment did not affect the reduction by CBD of the LPS-induced release of the proinflammatory cytokine IL-1β. CBD treatment modulates cholesterol homeostasis in microglial cells, and pretreatment with MBCD reverses this effect without interfering with CBD's anti-inflammatory effects. The effects of the CBD-induced increase in AEA accumulation on lipid-gene expression are discussed. SN - 1573-6830 UR - https://www.unboundmedicine.com/medline/citation/21533611/The_non_psychoactive_plant_cannabinoid_cannabidiol_affects_cholesterol_metabolism_related_genes_in_microglial_cells_ L2 - https://doi.org/10.1007/s10571-011-9692-3 DB - PRIME DP - Unbound Medicine ER -