Preferential limbic expression of the cannabinoid receptor mRNA in the human fetal brain

Wang, X; Dow-Edwards, Diana; Keller, Éva; Hurd, Yasmin L.

doi:10.1016/s0306-4522(03)00020-4

Cited by 129 publications

(94 citation statements)

References 31 publications

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“…RGS proteins are potent negative regulators of neurotransmitter signaling via G protein‐coupled receptors (Sjögren, 2011; Xie and Martemyanov, 2011). Among the G‐protein coupled receptors, the cannabinoid CB1 receptor is highly expressed in hippocampal CA regions (Wang et al , 2003). Furthermore, several RGS proteins are regulated in response to a different stimulus, e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Given that CB1 receptors are highly expressed in the hippocampal CA regions (Wang et al , 2003), which are essential for learning and short‐term as well as intermediate memory (Agis‐Balboa and Fischer, 2014), we focused on this region for the molecular characterization of the effects of adolescent exposure to WIN55212.2 on learning and memory during adulthood. Because the most prominent behavioral deficits reported in the current study were found in those animals chronically treated with either lowest or highest dose of the drug during adolescence, we directed further investigation on endocannabinoid content, epigenetic and transcriptional gene regulation level under these conditions.…”

Section: Introductionmentioning

confidence: 99%

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Chronic exposure to cannabinoids during adolescence causes long‐lasting behavioral deficits in adult mice

et al. 2016

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Regular use of marijuana during adolescence enhances the risk of long‐lasting neurobiological changes in adulthood. The present study was aimed at assessing the effect of long‐term administration of the synthetic cannabinoid WIN55212.2 during adolescence in young adult mice. Adolescent mice aged 5 weeks were subjected daily to the pharmacological action of WIN55212.2 for 3 weeks and were then left undisturbed in their home cage for a 5‐week period and finally evaluated by behavioral testing. Mice that received the drug during adolescence showed memory impairment in the Morris water maze, as well as a dose‐dependent memory impairment in fear conditioning. In addition, the administration of 3 mg/kg WIN55212.2 in adolescence increased adult hippocampal AEA levels and promoted DNA hypermethylation at the intragenic region of the intracellular signaling modulator Rgs7, which was accompanied by a lower rate of mRNA transcription of this gene, suggesting a potential causal relation. Although the concrete mechanisms underlying the behavioral observations remain to be elucidated, we demonstrate that long‐term administration of 3 mg/kg of WIN during adolescence leads to increased endocannabinoid levels and altered Rgs7 expression in adulthood and establish a potential link to epigenetic changes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic exposure to cannabinoids during adolescence causes long‐lasting behavioral deficits in adult mice

et al. 2016

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“…Our investigation on the effects of the in utero cannabis-exposure on mRNA expression was focused at the caudal level of the fetal forebrain in which the most intense CB 1 expression was located. 28 In the midgestational fetus, high PENK and PDYN mRNA expression levels were found primarily in the striatum; higher expression in the patch than the matrix compartment (Figure 1a and b). Preprodynorphin also had intense expression levels in the subthalamic nucleus (Figure 1b).…”

Section: Resultsmentioning

confidence: 96%

“…22 However, THC is known to activate multiple transcription factor genes including c-fos and CREB important for the regulation of the genes currently studied. 54,55 Moreover, the CB 1 mRNA has a high expression in the amygdala 28 and functional CB 1 binding sites are present in the putamen 3 of the human fetal brain. As such activation of the CB 1 signal transduction systems could regulate the expression levels of opioid-related genes within several structures observed in the present investigation.…”

Section: Discussionmentioning

confidence: 99%

“…7 During human fetal development, the CB 1 receptor is preferentially expressed in limbic-related structures such as the amygdala and hippocampus. 8 The CB 1 receptors have been strongly coupled to endogenous opioid systems especially in relation to reward and addictive behaviors. [9][10][11][12][13][14] The opioid system (endogenous ligands and receptors) is involved in a wide variety of neuronal functions including pain perception, cognition, emotional regulation and addictive behaviors (for a review see 15 ).…”

Section: Introductionmentioning

confidence: 99%

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Discrete opioid gene expression impairment in the human fetal brain associated with maternal marijuana use

et al. 2006

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Fetal development is a period sensitive to environmental influences such as maternal drug use. The most commonly used illicit drug by pregnant women is marijuana. The present study investigated the effects of in utero marijuana exposure on expression levels of opioid-related genes in the human fetal forebrain in light of the strong interaction between the cannabinoid and opioid systems. The study group consisted of 42 midgestation fetuses from saline-induced voluntary abortions. The opioid peptide precursors (preprodynorphin and preproenkephalin (PENK)) and receptor (mu, kappa and delta) mRNA expression were assessed in distinct brain regions. The effect of prenatal cannabis exposure was analyzed by multiple regression controlling for confounding variables (maternal alcohol and cigarette use, fetal age, sex, growth measure and post-mortem interval). Prenatal cannabis exposure was significantly associated with increased mu receptor expression in the amygdala, reduced kappa receptor mRNA in mediodorsal thalamic nucleus and reduced preproenkephalin expression in the caudal putamen. Prenatal alcohol exposure primarily influenced the kappa receptor mRNA with reduced levels in the amygdala, claustrum, putamen and insula cortex. No significant effect of prenatal nicotine exposure could be discerned in the present study group. These results indicate that maternal cannabis and alcohol exposure during pregnancy differentially impair opioid-related genes in distinct brain circuits that may have long-term effects on cognitive and emotional behaviors.

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Reduced Cortical Cannabinoid 1 Receptor Messenger RNA and Protein Expression in Schizophrenia

Eggan

Hashimoto²,

Lewis³

2008

Arch Gen Psychiatry

203

197

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Context Cannabis use is associated with both impaired cognitive functions, including working memory, and an increased risk of schizophrenia. Schizophrenia is characterized by impairments in working memory that are associated with reduced γ-aminobutyric acid (GABA) neurotransmission in the dorsolateral prefrontal cortex. The cannabinoid 1 receptor (CB1R) is highly expressed in the dorsolateral prefrontal cortex, is contained in the axon terminals of a subpopulation of perisomatic-targeting GABA neurons, and, when activated, suppresses the release of GABA. Objective To determine the potential relationship between CB1R signaling and altered GABA neurotransmission in schizophrenia by evaluating CB1R messenger RNA (mRNA) and protein expression in the dorsolateral pre-frontal cortex. Design In situ hybridization and immunocytochemistry techniques were used to examine the cortical levels of CB1R mRNA and protein, respectively. Setting Brain specimens were obtained from autopsies conducted at the Allegheny County Medical Examiner’s Office, Pittsburgh, Pennsylvania. Participants Postmortem brain specimens from 23 pairs of subjects with schizophrenia and age-, sex-, and postmortem interval–matched comparison subjects, as well as brain specimens from 18 macaque monkeys with long-term exposure to haloperidol, olanzapine, or placebo. Main Outcome Measures Optical density measures of CB1R mRNA expression and protein levels and correlations with previously reported glutamic acid decarboxylase 67 and cholecystokinin mRNA measures. Results Levels of CB1R mRNA were significantly lower by 14.8% in the subjects with schizophrenia. Similarly, CB1R protein levels, assessed by radioimmunocytochemistry and standard immunocytochemistry, were significantly decreased by 11.6% and 13.9%, respectively. Group differences in CB1R mRNA levels were significantly correlated with those in glutamic acid decarboxylase 67 and cholecystokinin mRNA levels. Expression of CB1R mRNA was not changed in antipsychotic-exposed monkeys, and neither CB1R mRNA levels nor protein levels were affected by potential confounding factors in the subjects with schizophrenia. Conclusions This combination of findings suggests the testable hypothesis that reduced CB1R mRNA and protein levels in schizophrenia represent a compensatory mechanism to increase GABA transmission from perisomatic-targeting cholecystokinin interneurons with impaired GABA synthesis.

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Preferential limbic expression of the cannabinoid receptor mRNA in the human fetal brain

Cited by 129 publications

References 31 publications

Chronic exposure to cannabinoids during adolescence causes long‐lasting behavioral deficits in adult mice

Chronic exposure to cannabinoids during adolescence causes long‐lasting behavioral deficits in adult mice

Discrete opioid gene expression impairment in the human fetal brain associated with maternal marijuana use

Reduced Cortical Cannabinoid 1 Receptor Messenger RNA and Protein Expression in Schizophrenia

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