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Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures

Abstract

Despite the widespread use of Cannabis as recreational drug or as medicine, little is known about its toxicity. The accumulation, metabolism and toxicity of THC were analyzed 10 days after a single treatment, and after repeated exposures during 10 days. Mixed-cell aggregate cultures of fetal rat telencephalon were used as in vitro model, as well as aggregates enriched either in neurons or in glial cells. It was found that THC accumulated preferentially in neurons, and that glia-neuron interactions decreased THC accumulation. The quantification of 11-OH-THC and of THC-COOH showed that brain aggregates were capable of THC metabolism. No cell-type difference was found for the metabolite 11-OH-THC, whereas the THC-COOH content was higher in mixed-cell cultures. No cell death was found at THC concentrations of 2 {mu}M in single treatment and of 1 {mu}M and 2 {mu}M in repeated treatments. Neurons, and particularly GABAergic neurons, were most sensitive to THC. Only the GABAergic marker was affected after the single treatment, whereas the GABAergic, cholinergic and astrocytic markers were decreased after the repeated treatments. JWH 015, a CB2 receptor agonist, showed effects similar to THC, whereas ACEA, a CB1 receptor agonist, had no effect. The expression of the cytokine IL-6 was upregulated  More>>
Authors:
Monnet-Tschudi, Florianne; [1]  Hazekamp, Arno; [2]  Perret, Nicolas; Zurich, Marie-Gabrielle; [1]  Mangin, Patrice; Giroud, Christian; [3]  Honegger, Paul [1] 
  1. Department of Physiology, University of Lausanne, 7, rue du Bugnon CH-1005 Lausanne (Switzerland)
  2. Department of Plant Metabolomics, University of Leiden (Netherlands)
  3. Laboratory of Forensic Toxicology and Chemistry, Institute of Legal Medicine, University Hospital Center and University of Lausanne (Switzerland)
Publication Date:
Apr 01, 2008
Product Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 228; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2007.11.007; PII: S0041-008X(07)00508-X; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BIOLOGICAL ACCUMULATION; BRAIN; CELL CULTURES; DRUGS; IN VITRO; METABOLISM; NERVE CELLS; RATS; RECEPTORS; TOXICITY
OSTI ID:
21140795
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0041-008X; TXAPA9; TRN: US08R3377020307
Availability:
Available from http://dx.doi.org/10.1016/j.taap.2007.11.007;INIS
Submitting Site:
INIS
Size:
page(s) 8-16
Announcement Date:
Mar 23, 2009

Citation Formats

Monnet-Tschudi, Florianne, Hazekamp, Arno, Perret, Nicolas, Zurich, Marie-Gabrielle, Mangin, Patrice, Giroud, Christian, and Honegger, Paul. Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures. United States: N. p., 2008. Web. doi:10.1016/j.taap.2007.11.007.
Monnet-Tschudi, Florianne, Hazekamp, Arno, Perret, Nicolas, Zurich, Marie-Gabrielle, Mangin, Patrice, Giroud, Christian, & Honegger, Paul. Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures. United States. doi:10.1016/j.taap.2007.11.007.
Monnet-Tschudi, Florianne, Hazekamp, Arno, Perret, Nicolas, Zurich, Marie-Gabrielle, Mangin, Patrice, Giroud, Christian, and Honegger, Paul. 2008. "Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures." United States. doi:10.1016/j.taap.2007.11.007. https://www.osti.gov/servlets/purl/10.1016/j.taap.2007.11.007.
@misc{etde_21140795,
title = {Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures}
author = {Monnet-Tschudi, Florianne, Hazekamp, Arno, Perret, Nicolas, Zurich, Marie-Gabrielle, Mangin, Patrice, Giroud, Christian, and Honegger, Paul}
abstractNote = {Despite the widespread use of Cannabis as recreational drug or as medicine, little is known about its toxicity. The accumulation, metabolism and toxicity of THC were analyzed 10 days after a single treatment, and after repeated exposures during 10 days. Mixed-cell aggregate cultures of fetal rat telencephalon were used as in vitro model, as well as aggregates enriched either in neurons or in glial cells. It was found that THC accumulated preferentially in neurons, and that glia-neuron interactions decreased THC accumulation. The quantification of 11-OH-THC and of THC-COOH showed that brain aggregates were capable of THC metabolism. No cell-type difference was found for the metabolite 11-OH-THC, whereas the THC-COOH content was higher in mixed-cell cultures. No cell death was found at THC concentrations of 2 {mu}M in single treatment and of 1 {mu}M and 2 {mu}M in repeated treatments. Neurons, and particularly GABAergic neurons, were most sensitive to THC. Only the GABAergic marker was affected after the single treatment, whereas the GABAergic, cholinergic and astrocytic markers were decreased after the repeated treatments. JWH 015, a CB2 receptor agonist, showed effects similar to THC, whereas ACEA, a CB1 receptor agonist, had no effect. The expression of the cytokine IL-6 was upregulated 48 h after the single treatment with 5 {mu}M of THC or JWH 015, whereas the expression of TNF-{alpha} remained unchanged. These results suggest that the adverse effects of THC were related either to THC accumulation or to cannabinoid receptor activation and associated with IL-6 upregulation.}
doi = {10.1016/j.taap.2007.11.007}
journal = {Toxicology and Applied Pharmacology}
issue = {1}
volume = {228}
place = {United States}
year = {2008}
month = {Apr}
}