Gene expression of circadian genes and CIART in bipolar disorder: A preliminary case-control study.

Based on the observed circadian rhythms disruptions and sleep abnormalities in bipolar disorders (BD), a chronobiological model has been proposed suggesting that core clock genes play a central role in the vulnerability to the disorder. In this context, the analysis of circadian genes expression levels is particularly relevant, however studies focused on the whole set of core clock genes are scarce. We compared the levels of expression of 19 circadian genes (including the recently described circadian repressor (CIART)) in 37 euthymic individuals with BD and 20 healthy controls (HC), using data obtained by RNA sequencing of lymphoblastoid cell lines and validated the results using RT-qPCR.

Transcriptomics and miRNomics data integration in lymphoblastoid cells highlights the key role of immune-related functions in lithium treatment response in Bipolar disorder.

Background: Bipolar Disorder (BD) is a complex mental disease characterized by recurrent episodes of mania and depression. Lithium (Li) represents the mainstay of BD pharmacotherapy, despite the narrow therapeutic index and the high variability in treatment response. However, although several studies have been conducted, the molecular mechanisms underlying Li therapeutic effects remain unclear.

Individual differences in cocaine-induced conditioned place preference in male rats: Behavioral and transcriptomic evidence.

Background: Substance use disorder emerges in a small proportion of drug users and has the characteristics of a chronic relapsing pathology.

Aims: Our study aimed to demonstrate and characterize the variability in the expression of the rewarding effects of cocaine in the conditioned place preference (CPP) paradigm.

Methods: A cocaine-CPP paradigm in male Sprague-Dawley rats with an extinction period of 12 days and reinstatement was conducted.

Methylomic Biomarkers of Lithium Response in Bipolar Disorder: A Proof of Transferability Study.

Response to lithium (Li) is highly variable in bipolar disorders (BD) and no clinical or biological predictors of long-term response have been validated to date. Using a genome-wide methylomic approach (SeqCapEpi), we previously identified seven differentially methylated regions (DMRs) that discriminated good from non-responders (prophylactic response phenotype defined using the "Alda" scale). This study is a proof of transferability from bench to bedside of this epigenetic signature.

Translational study of the whole transcriptome in rats and genetic polymorphisms in humans identifies LRP1B and VPS13A as key genes involved in tolerance to cocaine-induced motor disturbances.

Motor disturbances strongly increase the burden of cocaine use disorder (CUDs). The objective of our translational study was to identify the genes and biological pathways underlying the tolerance to cocaine-induced motor effects. In a 5-day protocol measuring motor tolerance to cocaine in rats (N = 40), modeling the motor response to cocaine in patients, whole-genome RNA sequencing was conducted on the ventral and dorsal striatum to prioritize a genetic association study in 225 patients with severe CUD who underwent thorough phenotypic (cocaine-induced hyperlocomotion, CIH; and cocaine-induced stereotypies, CIS) and genotypic [571,000 polymorphisms (SNPs)] characterization.

Selecting reference genes in RT-qPCR based on equivalence tests: a network based approach.

Because quantitative reverse transcription PCR (RT-qPCR) gene expression data are compositional, amounts of quantified RNAs must be normalized using reference genes. However, the two most used methods to select reference genes (NormFinder and geNorm) ignore the compositional nature of RT-qPCR data, and often lead to different results making reliable reference genes selection difficult. We propose a method, based on all pairwise equivalence tests on ratio of gene expressions, to select genes that are stable enough to be used as reference genes among a set a candidate genes.

Increased plasma levels of high mobility group box 1 protein in patients with bipolar disorder: A pilot study.

High mobility group box 1 (HMGB1) is a pro-inflammatory cytokine that emerges as a promising peripheral marker of inflammation. HMGB1 and C-reactive protein levels were assessed in plasma of control subjects and remitted patients with bipolar disorder (BD). HMGB1 levels were significantly higher in patients with BD as compared to control subjects whereas C-reactive protein levels did not differ between the two groups.

Determination of sets of covariating gene expression using graph analysis on pairwise expression ratios.

Motivation: RNA quantification experiments result in compositional data, however usual methods for compositional data analysis [additive log ratio (alr), centered log ratio (clr), isometric log ratio (ilr)] do not apply easily and give results difficult to interpret. To handle this, a method based on disjoint subgraphs in a graph whose nodes are the quantified RNAs is proposed. Edges in the graph are defined by lack of change in ratios of the corresponding RNAs between conditions.

Lithium response in bipolar disorder: No difference in GADL1 gene expression between cell lines from excellent-responders and non-responders.

Previous association studies have shown mixed results between glutamic acid decarboxylase like-1 (GADL1) gene polymorphism and prophylactic lithium response in bipolar disorder (BD) patients. In the present study, GADL1 gene expression was investigated in regard to lithium response, using Alda scale, in lymphoblastoid cells (LCLs) of 36 Caucasian BD patients. No difference in GADL1 expression was observed among LCLs from excellent-responders, non-responders or controls.

Lithium response in bipolar disorders and core clock genes expression.

Objectives: We examine whether the lithium response is associated with changes in the expression of core clock genes.

Methods: The effect of a therapeutic concentration of lithium (1 mM) on the expression levels of 17 circadian genes was examined in lymphoblastoid cell lines (LCLs) derived from two well-characterized groups of bipolar disorder patients, defined as lithium non-responders (NR, n = 20) or excellent responders (ER, n = 16). Quantitative real-time PCR (qRT-PCR) was conducted at 2, 4 and 8 days (d2, d4 and d8) with and without lithium exposure.

Impact of P-glycoprotein at the blood-brain barrier on the uptake of heroin and its main metabolites: behavioral effects and consequences on the transcriptional responses and reinforcing properties.

Rationale: Transport across the BBB is a determinant of the rate and extent of drug distribution in the brain. Heroin exerts its effects through its principal metabolites 6-monoacetyl-morphine (6-MAM) and morphine. Morphine is a known substrate of P-glycoprotein (P-gp) at the blood-brain-barrier (BBB) however, little is known about the interaction of heroin and 6-MAM with P-gp.

Comparison of the transcriptional responses induced by acute morphine, methadone and buprenorphine.

Despite their widespread use in opioid maintenance treatment and pain management, little is known about the intracellular effectors of methadone and buprenorphine and the transcriptional responses they induce. We therefore studied the acute effects of these two opioids in rats, comparing our observations with those for the reference molecule, morphine. We determined the analgesic ED50 of the three molecules in the tail flick test, to ensure that transcriptional effects were compared between doses of equivalent analgesic effect.

Characteristics of dual specificity phosphatases mRNA regulation by 3,4-methylenedioxymethamphetamine acute treatment in mice striatum.

3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug that has rewarding properties in rodents but little is known about its effects at the cellular and molecular levels. We have previously shown that the ERK pathway is important for the regulation in gene expression observed in mice striatum after acute treatment with MDMA. Interestingly, three dual specificity phosphatases were found among the genes modulated by MDMA acute treatment.

Involvement of D1 dopamine receptor in MDMA-induced locomotor activity and striatal gene expression in mice.

3,4-Methylenedioxymethamphetamine (MDMA), a widely used recreational drug with psychoactive properties, induces both serotonin and dopamine release in the brain. In rats and mice MDMA induces behavioural changes and has rewarding effects but little is known about its cellular effects. We have previously shown that the ERK pathway is important for the changes in gene expression observed in mice striatum after treatment with this psychostimulant.

Rnd family genes are differentially regulated by 3,4-methylenedioxymethamphetamine and cocaine acute treatment in mice brain.

Drugs of abuse induce alterations in cytoskeletal and cytoskeleton associated genes in several brain areas. We have previously shown that acute MDMA regulates the mRNA level of Rnd3, a Rho GTPase involved in actin cytoskeleton regulation, in mice striatum. In this study we investigated the effects of single administration of cocaine, another psychostimulant with a slightly different mechanism of action, on the mRNA levels of the three members of the Rnd genes family (Rnd1, Rnd2 and Rnd3).

Sensitization to the conditioned rewarding effects of morphine modulates gene expression in rat hippocampus.

Opiates addiction is characterized by its long-term persistence. In order to study the enduring changes in long-term memory in hippocampus, a pivotal region for this process, we used suppression subtractive hybridization to compare hippocampal gene expression in morphine and saline-treated rats. Animals were subjected to an extended place preference paradigm consisting of four conditioning phases.

Regulation of genes involved in dopamine transporter modulation by acute cocaine in rat striatum.

It is well established that acute administration of psychostimulants alters dopamine transport. However, the exact mechanism of this modulation is still unknown. In this study we examined the mRNA levels of several proteins involved in the various proposed processes following cocaine administration.

Cytoskeletal genes regulation by chronic morphine treatment in rat striatum.

It has been previously suggested that morphine can regulate the expression and function of some proteins of the cytoskeleton. In the present study, we used real-time quantitative polymerase chain reaction to examine the effects of chronic morphine administration, in rat striatum, on 14 proteins involved in microtubule polymerization and stabilization, intracellular trafficking, and serving as markers of neuronal growth and degeneration. Chronic morphine treatment led to modulation of the mRNA level of seven of the 14 genes tested.

Fos but not Cart (cocaine and amphetamine regulated transcript) is overexpressed by several drugs of abuse: a comparative study using real-time quantitative polymerase chain reaction in rat brain.

It has been reported that cocaine and amphetamine-regulated transcript (Cart) peptides can increase locomotor activity and produce a conditioned place preference. To establish whether or not Cart can be consider as a valuable marker of addiction we performed a comparative study of the expression of Cart and Fos genes by several drugs of abuse. This was achieved using real-time quantitative polymerase chain reaction in four rat brain structures: prefrontal cortex, caudate putamen, nucleus accumbens and hippocampus.