Dataset Information

Differential expression and functional role of cannabinoid genes in alcohol users.

ABSTRACT: Genetic factors account for about fifty percent of the risk for alcoholism and alcohol dependence (AD) has been reported to be influenced by cannabinoid receptors (CBRs) and the endocannabinoid system (ECS). Previous studies have focused on cannabinoids and alcohol-related effects in the CNS; however, the role CBRs play on alcohol effects in the immune system has not been elucidated yet. Since alcohol can affect immune responses and have detrimental effects on immune cells such as dendritic cells (DCs), we hypothesize that alcohol can exert its effects on DCs by modulating changes in CBRs, which in turn can regulate important DC functions such as cytokine production.Therefore, we studied the expression of CNR1 and CNR2, and the novel cannabinoid G protein-coupled receptor (GPCR) 55 (GPR55) in human monocyte-derived dendritic cells (MDDCs) from alcohol users. CNR1, CNR2, and GPR55 genes were measured by qRT-PCR and protein by flow cytometry. MDDCs from alcohol users show significantly higher levels of CNR2 and GPR55 compared to MDDCs from non-users. These findings were further confirmed using MDDCs treated with alcohol. Inflammatory cytokines were measured in EtOH-treated and non-treated cells by antibody array.Functional effects of CBRs on MDDCs were shown by CB2 and GPR55 siRNA transfection. Transfected EtOH-treated cells showed significantly higher levels of proinflammatory cytokine production as measured by IL-1? expression. Our results provide insights into alcohol mechanisms of DC regulation and show, for the first time, that alcohol is inducing CNR2 and GPR55 in human DCs.

SUBMITTER: Agudelo M

PROVIDER: S-EPMC3818789 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Differential expression and functional role of cannabinoid genes in alcohol users.

Agudelo Marisela M Yndart Adriana A Morrison Marisol M Figueroa Gloria G Muñoz Karla K Samikkannu Thangavel T Nair Madhavan P MP

Drug and alcohol dependence 20130905 2

<h4>Background</h4>Genetic factors account for about fifty percent of the risk for alcoholism and alcohol dependence (AD) has been reported to be influenced by cannabinoid receptors (CBRs) and the endocannabinoid system (ECS). Previous studies have focused on cannabinoids and alcohol-related effects in the CNS; however, the role CBRs play on alcohol effects in the immune system has not been elucidated yet. Since alcohol can affect immune responses and have detrimental effects on immune cells suc ...[more]

PMID: 24060590

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Project description:Background: The endocannabinoid system is present in multiple organ systems and is involved in smooth muscle regulation, immune function, neuroendocrine modulation, and metabolism of tissues. Limited data are available regarding the presence and role of this system in reproductive tissues. Components of the endocannabinoid system have been identified in myometrial and placental tissues. However, no study has investigated differential expression of the endocannabinoid system in labor. Objectives: The purpose of this study was to identify and quantify two components of the endocannabinoid system, the CB1 cannabinoid receptor and cannabinoid receptor interacting protein 1a (CRIP1a) in uterine and placental tissues, and to determine if there is differential expression in tissues exposed to labor. We hypothesized that CB1 cannabinoid receptor concentration would be altered in uterine and placental tissue exposed to labor compared with tissues not exposed to labor. Study Design: Uterine and placental tissue samples were collected in nine laboring and 11 nonlaboring women undergoing cesarean delivery. CB1 cannabinoid receptor and CRIP1a presence and quantification were evaluated using western blot, immunohistochemistry, and real-time quantitative polymerase chain reaction. Statistical comparisons of laboring and nonlaboring subjects were made for uterine and placental tissue using a Mann-Whitney test. Results: Immunohistochemistry demonstrated positive staining for CB1 cannabinoid receptors and CRIP1a in uterine tissue. The protein abundance of CB1 cannabinoid receptor in uterine tissue was significantly lower in tissues exposed to labor (p=0.01). The protein abundance of CRIP1a was lower in uterine tissue exposed to labor but did not reach statistical significance (p=0.06). mRNA expression of CB1 cannabinoid receptor (p=0.20) and CRIP1a (p=0.63) did not differ in labored compared with nonlabored uterine tissues. Conclusions: Our findings of diminished protein density of CB1 cannabinoid receptor in uterine tissue exposed to labor support the hypothesis that the endocannabinoid system plays a role in parturition. Our data add to the growing body of evidence indicating the endocannabinoid system is of importance for successful reproduction and support the need for additional research investigating this complex system as it pertains to labor. ClinicalTrials.gov ID: NCT03752021.

Project description:Alcohol and nicotine intake result in neurological alterations at the circuit level. Resting state functional connectivity has shown great potential in identifying these alterations. However, current studies focus on specific seeds and leave out many brain regions where effects might exist. The present study uses a data driven technique for brain segmentation covering the whole brain. Functional magnetic-resonance-imaging (fMRI) data were collected from 188 subjects:51 non-substance consumption controls (CTR), 36 smoking-and-drinking subjects (SAD), 28 drinkers (DRN), and 73 smokers (SMK). Data were processed using group independent component analysis to derive resting state networks (RSN). The resting state functional network connectivity (rsFNC) was then calculated through correlation between time courses. One-way ANOVA tests were used to detect rsFNC differences among the four groups. A total of 50 ANOVA tests were significant after multi-comparison correction. Results delineate a general pattern of hypo-connectivity in the substance consumers. Precuneus, postcentral gyrus, insula and visual cortex were the main brain areas with rsFNC reduction suggesting reduced interoceptive awareness in drinkers. In addition, connectivity reduction between postcentral and one RSN covering right fusiform and lingual gyri showed significant association with severity of hazardous drinking. In smokers, connectivity changes agreed with the idea of a shift towards endogenous information processing, represented by the DMN. Hypo-connectivity between thalamus and putamen was observed in smokers. In contrast, the angular gyrus showed hyper-connectivity with the precuneus linked to smoking and significantly correlated with nicotine dependence severity. In spite of the presence of common effects, our results suggest that particular effects of alcohol and nicotine can be separated and identified. Results also suggest that concurrent use of both substances affects brain connectivity in a complex manner, requiring careful consideration of interaction effects.

Dataset Information

Differential expression and functional role of cannabinoid genes in alcohol users.

Publications

Differential expression and functional role of cannabinoid genes in alcohol users.

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